Trial Outcomes & Findings for A Study of Pemetrexed, Carboplatin and Bevacizumab in Participants With Nonsquamous Non-Small Cell Lung Cancer (NCT NCT00762034)
NCT ID: NCT00762034
Last Updated: 2015-12-21
Results Overview
Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
939 participants
Primary outcome timeframe
Baseline to date of death from any cause (up to 37.06 months)
Results posted on
2015-12-21
Participant Flow
Participant milestones
| Measure |
Pem/Carbo/Bev
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|
|
Induction Period
STARTED
|
472
|
467
|
|
Induction Period
Received at Least 1 Dose of Study Drug
|
442
|
443
|
|
Induction Period
COMPLETED
|
294
|
298
|
|
Induction Period
NOT COMPLETED
|
178
|
169
|
|
Maintenance Period
STARTED
|
294
|
298
|
|
Maintenance Period
Received at Least 1 Dose of Study Drug
|
294
|
298
|
|
Maintenance Period
COMPLETED
|
0
|
0
|
|
Maintenance Period
NOT COMPLETED
|
294
|
298
|
Reasons for withdrawal
| Measure |
Pem/Carbo/Bev
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|
|
Induction Period
Protocol Violation
|
1
|
2
|
|
Induction Period
Entry Criterion Not Met
|
12
|
11
|
|
Induction Period
Adverse Event
|
27
|
38
|
|
Induction Period
Lost to Follow-up
|
1
|
1
|
|
Induction Period
Progressive Disease
|
73
|
55
|
|
Induction Period
Physician Decision
|
21
|
20
|
|
Induction Period
Withdrawal by Subject
|
15
|
19
|
|
Induction Period
Deaths Not Due to Study Disease
|
19
|
14
|
|
Induction Period
Deaths Due to Study Disease
|
9
|
9
|
|
Maintenance Period
Protocol Violation
|
1
|
3
|
|
Maintenance Period
Entry Criterion Not Met
|
0
|
2
|
|
Maintenance Period
Adverse Event
|
42
|
26
|
|
Maintenance Period
Progressive Disease
|
186
|
224
|
|
Maintenance Period
Physician Decision
|
25
|
20
|
|
Maintenance Period
Withdrawal by Subject
|
34
|
14
|
|
Maintenance Period
Death not due to study disease
|
2
|
5
|
|
Maintenance Period
Death due to study disease
|
3
|
3
|
|
Maintenance Period
Other
|
1
|
1
|
Baseline Characteristics
A Study of Pemetrexed, Carboplatin and Bevacizumab in Participants With Nonsquamous Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Pem/Carbo/Bev
n=472 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=467 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Total
n=939 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
<=65 years
|
249 participants
n=5 Participants
|
236 participants
n=7 Participants
|
485 participants
n=5 Participants
|
|
Age, Customized
>65 years
|
223 participants
n=5 Participants
|
231 participants
n=7 Participants
|
454 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
221 Participants
n=5 Participants
|
218 Participants
n=7 Participants
|
439 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
251 Participants
n=5 Participants
|
249 Participants
n=7 Participants
|
500 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
409 participants
n=5 Participants
|
396 participants
n=7 Participants
|
805 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
42 participants
n=5 Participants
|
52 participants
n=7 Participants
|
94 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
15 participants
n=5 Participants
|
14 participants
n=7 Participants
|
29 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple race/ethnicities
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Information not provided
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
472 participants
n=5 Participants
|
467 participants
n=7 Participants
|
939 participants
n=5 Participants
|
|
Previously Treated Brain Metastasis
Yes
|
52 participants
n=5 Participants
|
52 participants
n=7 Participants
|
104 participants
n=5 Participants
|
|
Previously Treated Brain Metastasis
No
|
420 participants
n=5 Participants
|
415 participants
n=7 Participants
|
835 participants
n=5 Participants
|
|
Histological Subtype
Adenocarcinoma, Lung
|
367 participants
n=5 Participants
|
360 participants
n=7 Participants
|
727 participants
n=5 Participants
|
|
Histological Subtype
Bronchioalveolar Carcinoma
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Histological Subtype
Large Cell Lung Carcinoma
|
8 participants
n=5 Participants
|
15 participants
n=7 Participants
|
23 participants
n=5 Participants
|
|
Histological Subtype
NSCLC Not Otherwise Specified
|
47 participants
n=5 Participants
|
39 participants
n=7 Participants
|
86 participants
n=5 Participants
|
|
Histological Subtype
NSCLC Poorly Differentiated
|
39 participants
n=5 Participants
|
47 participants
n=7 Participants
|
86 participants
n=5 Participants
|
|
Histological Subtype
Predominantly Adenocarcinoma
|
7 participants
n=5 Participants
|
2 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Histological Subtype
Unknown
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Histological Category for Subgroup Analyses
Adenocarcinoma
|
378 participants
n=5 Participants
|
365 participants
n=7 Participants
|
743 participants
n=5 Participants
|
|
Histological Category for Subgroup Analyses
Large Cell Carcinoma
|
8 participants
n=5 Participants
|
15 participants
n=7 Participants
|
23 participants
n=5 Participants
|
|
Histological Category for Subgroup Analyses
Other or Indeterminant
|
86 participants
n=5 Participants
|
86 participants
n=7 Participants
|
172 participants
n=5 Participants
|
|
Histological Category for Subgroup Analyses
Unknown
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to date of death from any cause (up to 37.06 months)Population: All randomized participants using the intent-to-treat principle. Number of participants censored: n=131, 127 in Pem/Carbo/Bev and Pac/Carbo/Bev arms, respectively.
Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=472 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=467 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Overall Survival
|
12.55 months
Interval 11.3 to 14.03
|
13.40 months
Interval 11.86 to 14.91
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease (up to 37.06 months)Population: All randomized participants using the intent-to-treat principle
Overall Response Rate (ORR) is the number of participants with a Complete Response (CR) and Partial Response (PR) divided by the total number of randomized participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.0) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared to baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=472 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=467 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Percentage of Participants With a Complete Response (CR) and Partial Response (PR) (Overall Response Rate)
|
34.1 percentage of participants
Interval 29.8 to 38.6
|
33.0 percentage of participants
Interval 28.7 to 37.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease (up to 37.06 months)Population: All randomized participants using the intent-to-treat principle
Disease Control Rate (DCR) is the number of participants with a Complete Response (CR), Partial Response (PR), and Stable Disease (SD) divided by the total number of randomized participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.0) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared with baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions compared with the smallest sum of the longest diameter recorded since the start of treatment or the appearance of 1 or more new lesion(s). Stable Disease (SD) was defined as small changes that did not meet above criteria.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=472 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=467 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Percentage of Participants With a Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate)
|
65.9 percentage of participants
Interval 61.4 to 70.2
|
69.8 percentage of participants
Interval 65.4 to 73.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease or date of death from any cause (up to 33.54 months)Population: All randomized participants using the intent-to-treat principle. Number of participants censored: n=127, 109 in Pem/Carbo/Bev and Pac/Carbo/Bev arms, respectively.
Progression free survival (PFS) is defined as the time from date of randomization to the date of objective disease progression or death due to any cause. Participants were censored at date of last PFS assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy, whichever was earlier.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=472 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=467 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Progression Free Survival Time
|
6.04 months
Interval 5.55 to 6.87
|
5.55 months
Interval 5.39 to 5.98
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease (up to 37.06 months)Population: All randomized participants using the intent-to-treat principle. Number of participants censored: n=198, 172 in Pem/Carbo/Bev and Pac/Carbo/Bev arms, respectively.
Time to progressive disease was defined as the time from randomization to the first date of objective disease progression. Participants were censored at date of last PFS assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy, whichever was earlier.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=472 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=467 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Time to Progressive Disease
|
7.03 months
Interval 6.24 to 8.05
|
6.04 months
Interval 5.58 to 6.87
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to study endpoint (up to 37.06 months)Population: All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
Safety and toxicity profile was defined as serious and other non-serious adverse events. A summary of serious and all other non-serious adverse events is located in the Reported Adverse Event module.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=442 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=292 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
n=443 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
n=298 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Safety and Toxicity Profile of Study Treatments
Serious Adverse Events (SAEs)
|
111 participants
|
83 participants
|
123 participants
|
68 participants
|
|
Safety and Toxicity Profile of Study Treatments
Other Adverse Events (AEs)
|
432 participants
|
288 participants
|
431 participants
|
296 participants
|
SECONDARY outcome
Timeframe: Baseline to study endpoint (up to 37.06 months)Population: All randomized participants who received at least 1 dose of study drug and had at least one hospitalization while on study or within 30 days of discontinuation.
Length of hospitalization in participants hospitalized during the study or within 30 days of discontinuation regardless of whether the hospitalization was or was not due to study drug.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=177 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=172 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Duration of Hospitalizations Per Participant
|
9.4 days
Standard Deviation 9.8
|
8.0 days
Standard Deviation 6.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to study endpoint (up to 37.06 months)Population: All randomized participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=442 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=443 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Number of Participants Who Received a Transfusion
|
116 participants
|
44 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to study endpoint (up to 37.06 months)Population: All randomized participants
Outcome measures
| Measure |
Pem/Carbo/Bev
n=472 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=467 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Number of Participants Receiving Concomitant Medication
|
406 participants
|
421 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to first 10 cycles (4 induction and 6 maintenance cycles, cycle=21 days)Population: The LMM analysis includes data from all participants in each arm for whom a validated translation is available in a language in which the completer (participant) is fluent and have evaluable FACT-G data, using the intent-to-treat principle.
The FACT-G is a validated instrument used to measure quality of life (QOL) in participants with cancer consisting of the 27-item questionnaire and is organized into subscales, each designed to assess a QOL domain: physical well-being (PWB)-7 items; social/family well-being (SWB)-7 items; emotional well-being (EWB)-6 items; functional well-being (FWB)-7 items. Each item uses a 5 point rating scale (0="not at all" and 4=equals "very much"). FACT-G Total is the sum of the scores of all 4 subscales and ranges from 0 to 108. Higher scores indicate better QOL. Least squares mean (LSmean) change is calculated using the linear-mixed model (LMM) analysis controlled for treatment, baseline value, time point and treatment by time point interaction.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=472 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=462 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy - General (FACT-G)
|
0.51 units on a scale
Standard Error 0.54
|
0.18 units on a scale
Standard Error 0.54
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to first 10 cycles (4 induction and 6 maintenance cycles, cycle=21 days)Population: The LMM analysis includes data from all participants in each arm for whom a validated translation is available in a language in which the completer (participant) is fluent and have evaluable FACT-L, using the intent-to-treat principle.
FACT-L is a valid instrument used to measure quality of life (QOL) in participants with cancer consisting of the 27-item FACT-General (G) and 9-item lung cancer subscale (LCS). FACT-G is organized into subscales: physical well-being (PWB)-7 items; social/family well-being (SWB)-7 items; emotional well-being (EWB)-6 items; functional well-being (FWB)-7 items. Each item uses a 5 point rating scale (0="not at all" and 4=equals "very much"). FACT-L Total Score=4 subscales + LCS and ranges from 0 to 144. Trial Outcome Index-Lung (TOI-L)=PWB+FWB+LCS and ranges from 0 to 92. Higher scores indicate better QOL. Least squares mean (LSmean) change is calculated using the linear-mixed model (LMM) analysis controlled for treatment, baseline value, time point and treatment by time point interaction.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=472 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=467 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy - Lung (FACT-L)
FACT-L Total Score (n=397, 392)
|
1.88 units on a scale
Standard Error 0.65
|
1.66 units on a scale
Standard Error 0.66
|
—
|
—
|
|
Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy - Lung (FACT-L)
Trial Outcome Index-Lung (TOI-L) (n=396, 394)
|
-0.38 units on a scale
Standard Error 0.50
|
-0.40 units on a scale
Standard Error 0.50
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to first 10 cycles (4 induction and 6 maintenance cycles, cycle=21 days)Population: The LMM analysis includes data from all participants in each arm for whom a validated translation is available in a language in which the completer (participant) is fluent and have evaluable FACT/GOG-Ntx data, using the intent-to-treat principle.
FACT/GOG-Ntx is a validated instrument used to measure quality of life (QOL) in participants with cancer and neurotoxicity (Ntx) consisting of 27-item FACT-General (G) and 11-item Ntx subscale. FACT-G is organized into domain subscales: physical well-being (PWB)-7 items; social/family well-being (SWB)-7 items; emotional well-being (EWB)-6 items; functional well-being (FWB)-7 items; each uses a 5 point rating scale (0="not at all" and 4=equals "very much"). FACT/GOG-Ntx Total Score=sum 5 subscales and ranges from 0-152. Ntx Trial Outcome Index (TOI-Ntx)=PWB+FWB+NTX and range from 0-100. For all FACT scales, higher scores indicate better QOL. Least squares mean (LSmean) change is calculated using the linear-mixed model (LMM) analysis controlled for treatment, baseline value, time point and treatment by time point interaction.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=472 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=467 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group- Neurotoxicity (FACT/GOG-Ntx)
FACT/GOG-Ntx Total Score (n=393, 389)
|
-0.60 units on a scale
Standard Error 0.70
|
-5.48 units on a scale
Standard Error 0.70
|
—
|
—
|
|
Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group- Neurotoxicity (FACT/GOG-Ntx)
Ntx Trial Outcome Index (TOI-Ntx)(n=393, 390)
|
-2.79 units on a scale
Standard Error 0.55
|
-7.60 units on a scale
Standard Error 0.55
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)Population: Participants who were randomized to Pem/Carbo/Bev, who received study drug, and had evaluable Cmax data.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=14 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Pemetrexed
|
122 micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 20
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)Population: Participants who were randomized to Pem/Carbo/Bev, who received study drug, and had evaluable t1/2 data.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=15 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Elimination Half-life (t1/2) for Pemetrexed
|
2.88 hours (hr)
Geometric Coefficient of Variation 13
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)Population: Participants who were randomized to Pem/Carbo/Bev, who received study drug, and had evaluable AUC(0-∞) data.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=15 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) for Pemetrexed
|
203 microgram*hour per milliliter (μg•hr/mL)
Geometric Coefficient of Variation 23
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)Population: Participants who were randomized to Pem/Carbo/Bev, who received study drug, and had evaluable CL data.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=15 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Pemetrexed Clearance (CL)
|
72.1 milliliters per minute (mL/min)
Geometric Coefficient of Variation 25
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)Population: Randomized participants who received study drug and had evaluable Cmax data.
Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=20 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=16 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Total (Bound and Unbound) Platinum and Unbound Platinum
Total (Bound and Unbound)
|
18.4 micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 24
|
17.8 micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 33
|
—
|
—
|
|
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Total (Bound and Unbound) Platinum and Unbound Platinum
Unbound (n=18, 15)
|
21.1 micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 31
|
17.1 micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 34
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)Population: Randomized participants who received study drug and had evaluable t1/2 data.
Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=18 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=16 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Elimination Half-life (t1/2) for Total (Bound and Unbound) Platinum and Unbound Platinum
Total (Bound and Unbound)
|
65.6 hours (hr)
Geometric Coefficient of Variation 69
|
86.4 hours (hr)
Geometric Coefficient of Variation 21
|
—
|
—
|
|
Pharmacokinetics (PK): Elimination Half-life (t1/2) for Total (Bound and Unbound) Platinum and Unbound Platinum
Unbound (n=17, 13)
|
2.03 hours (hr)
Geometric Coefficient of Variation 15
|
1.95 hours (hr)
Geometric Coefficient of Variation 21
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)Population: Randomized participants who received study drug and had evaluable AUC(0-∞) data.
Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=18 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=16 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) for Total (Bound and Unbound) Platinum and Unbound Platinum
Total (Bound and Unbound)
|
160 microgram*hour per milliliter (μg•hr/mL)
Geometric Coefficient of Variation 32
|
182 microgram*hour per milliliter (μg•hr/mL)
Geometric Coefficient of Variation 24
|
—
|
—
|
|
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) for Total (Bound and Unbound) Platinum and Unbound Platinum
Unbound (n=17, 13)
|
55.7 microgram*hour per milliliter (μg•hr/mL)
Geometric Coefficient of Variation 33
|
62.9 microgram*hour per milliliter (μg•hr/mL)
Geometric Coefficient of Variation 34
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)Population: Randomized participants who received study drug and had evaluable CL data.
Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=18 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=16 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Platinum Clearance (CL) for Total (Bound and Unbound) and Unbound Forms
Total (Bound and Unbound)
|
2.02 liters per hour (L/hr)
Geometric Coefficient of Variation 39
|
1.87 liters per hour (L/hr)
Geometric Coefficient of Variation 28
|
—
|
—
|
|
Pharmacokinetics (PK): Platinum Clearance (CL) for Total (Bound and Unbound) and Unbound Forms
Unbound (n=17, 13)
|
5.81 liters per hour (L/hr)
Geometric Coefficient of Variation 35
|
5.36 liters per hour (L/hr)
Geometric Coefficient of Variation 47
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)Population: Randomized participants who received study drug and had evaluable Cmax data.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=20 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=16 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Bevacizumab
|
276 micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 18
|
302 micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 20
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)Population: Randomized participants who received study drug and had evaluable t1/2 data.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=17 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=16 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Elimination Half-life (t1/2) for Bevacizumab
|
14.8 days
Geometric Coefficient of Variation 36
|
12.8 days
Geometric Coefficient of Variation 46
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)Population: Randomized participants who received study drug and had evaluable AUC(0-∞) data.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=17 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=16 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) Bevacizumab
|
3070 microgram*day per milliliter (μg•day/mL)
Geometric Coefficient of Variation 29
|
3160 microgram*day per milliliter (μg•day/mL)
Geometric Coefficient of Variation 33
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)Population: Randomized participants who received study drug and had evaluable CL data.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=17 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=16 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Bevacizumab Clearance (CL)
|
0.341 liters per day (L/day)
Geometric Coefficient of Variation 31
|
0.376 liters per day (L/day)
Geometric Coefficient of Variation 38
|
—
|
—
|
SECONDARY outcome
Timeframe: BaselinePopulation: All randomized participants with EGFR data regardless of study treatment.
Epidermal Growth Factor Receptor (EGFR) mutations were measured by polymerase chain reaction (PCR).
Outcome measures
| Measure |
Pem/Carbo/Bev
n=132 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Translational Research: Number of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations
EGFR mutation positive
|
11 participants
|
—
|
—
|
—
|
|
Translational Research: Number of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations
EGFR mutation negative
|
121 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to date of death from any cause (up to 37.06 months)Population: All randomized participants with TTF-1 H scores regardless of study treatment. Participants censored: n=38, 11 in the TTF-1 Nuclear Positive and Negative arms, respectively.
Nuclear Thyroid Transcription Factor-1 (TTF-1) expression was measured using an Immunohistochemistry (IHC) assay which were scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system, and H score is a calculated using formula: 1x(percentage of cells stained 1+) + 2x(percentage of cells stained 2+) + 3x(percentage of cells stained 3+). TTF-1 Positive have an H score \>0 and TTF-1 Negative have an H score=0. Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=139 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=66 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Translational Research: Overall Survival (OS) Based on Nuclear Thyroid Transcription Factor-1 (TTF-1) Expression Regardless of Study Treatment
|
14.9 months
Interval 12.8 to 17.6
|
8.7 months
Interval 6.4 to 10.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to date of death from any cause (up to 37.06 months)Population: All randomized participants with TS Cytoplasm and Nucleus H scores. Participants censored: TS Cytoplasm Positive n=23, 20 and Negative n=4, 1; TS Nucleus Positive n=17, 9 and Negative n=10, 12 for the Pem/Carbo/Bev and Pac/Carbo/Bev arms, respectively.
Cytoplasmic and nuclear Thymidylate Synthase (TS) expression was measured using an Immunohistochemistry (IHC) assay which were scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic and nuclear staining, and H score was calculated using formula: 1x(percentage of cells stained 1+) + 2x(percentage of cells stained 2+) + 3x(percentage of cells stained 3+). TS Positive have an H score \>0 and TS Negative have an H score=0. Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=100 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=89 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Translational Research: Overall Survival (OS) Based on Cytoplasmic and Nuclear Thymidylate Synthase (TS) Expression
TS Cytoplasm Positive (H score > 0; n=90, 83)
|
12.9 months
Interval 10.8 to 16.9
|
12.4 months
Interval 10.9 to 15.5
|
—
|
—
|
|
Translational Research: Overall Survival (OS) Based on Cytoplasmic and Nuclear Thymidylate Synthase (TS) Expression
TS Cytoplasm Negative (H score = 0; n=10, 6)
|
18.2 months
Interval 12.5 to
Not calculable due to the low number of participants reaching endpoint event of death.
|
11.6 months
Interval 9.1 to 14.7
|
—
|
—
|
|
Translational Research: Overall Survival (OS) Based on Cytoplasmic and Nuclear Thymidylate Synthase (TS) Expression
TS Nucleus Positive (H score > 0; n=68, 51)
|
12.7 months
Interval 9.7 to 15.4
|
12.4 months
Interval 8.4 to 15.5
|
—
|
—
|
|
Translational Research: Overall Survival (OS) Based on Cytoplasmic and Nuclear Thymidylate Synthase (TS) Expression
TS Nucleus Negative (H score = 0; n=32, 38)
|
19.2 months
Interval 12.5 to 24.1
|
12.4 months
Interval 10.1 to 17.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to date of death from any cause (up to 37.06 months)Population: All randomized participants with FR-α Cytoplasm or Membrane H scores. Participants censored: FR-α Positive Cytoplasm n=21, 15 and Negative n=4, 3; FR-α Membrane Positive n=16, 8 and Negative n=9, 10 for Pem/Carbo/Bev and Pac/Carbo/Bev arms, respectively.
Cytoplasmic and membrane Folate Receptor Alpha (FR-α) expression was measured using an Immunohistochemistry (IHC) assay which were scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic or membrane staining, and H score is a calculated using formula: 1x(percentage of cells stained 1+) + 2x(percentage of cells stained 2+) + 3x(percentage of cells stained 3+). FR-α Positive have an H score \>0 and FR-α Negative have an H score=0. Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive.
Outcome measures
| Measure |
Pem/Carbo/Bev
n=98 Participants
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev
n=82 Participants
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Induction Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
Pac/Carbo/Bev; Maintenance Phase
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m\^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
|
|---|---|---|---|---|
|
Translational Research: Overall Survival (OS) Based on Cytoplasmic and Membrane Folate Receptor Alpha (FR-α) Expression
FR-α Cytoplasm Positive (H score > 0; n=64, 53)
|
14.4 months
Interval 11.4 to 22.2
|
14.3 months
Interval 11.2 to 18.2
|
—
|
—
|
|
Translational Research: Overall Survival (OS) Based on Cytoplasmic and Membrane Folate Receptor Alpha (FR-α) Expression
FR-α Cytoplasm Negative (H score = 0; n=34, 29)
|
12.0 months
Interval 9.6 to 16.9
|
11.2 months
Interval 5.7 to 14.4
|
—
|
—
|
|
Translational Research: Overall Survival (OS) Based on Cytoplasmic and Membrane Folate Receptor Alpha (FR-α) Expression
FR-α Membrane Positive (H score > 0; n=39, 22)
|
19.2 months
Interval 10.5 to 30.8
|
15.5 months
Interval 11.2 to
Not calculable due to the low number of participants reaching endpoint event of death.
|
—
|
—
|
|
Translational Research: Overall Survival (OS) Based on Cytoplasmic and Membrane Folate Receptor Alpha (FR-α) Expression
FR-α Membrane Negative (H score = 0; n=59, 60)
|
12.9 months
Interval 9.6 to 16.7
|
11.3 months
Interval 8.8 to 14.7
|
—
|
—
|
Adverse Events
Pem/Carbo/Bev
Serious events: 188 serious events
Other events: 430 other events
Deaths: 0 deaths
Pac/Carbo/Bev
Serious events: 181 serious events
Other events: 433 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pem/Carbo/Bev
n=442 participants at risk
Induction:
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
Maintenance:
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
|
Pac/Carbo/Bev
n=443 participants at risk
Induction:
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m ²) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
Maintenance:
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
4.1%
18/442 • Number of events 50
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
1.1%
5/443 • Number of events 10
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.4%
6/442 • Number of events 7
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
2.9%
13/443 • Number of events 13
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Haemorrhagic anaemia
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.68%
3/442 • Number of events 7
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Microangiopathic haemolytic anaemia
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.3%
10/442 • Number of events 15
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
2.0%
9/443 • Number of events 9
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.68%
3/442 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.7%
12/442 • Number of events 20
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Angina pectoris
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Atrial fibrillation
|
0.23%
1/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Atrial flutter
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Cardiac arrest
|
0.68%
3/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.68%
3/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Cardiomegaly
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Cardiomyopathy
|
0.23%
1/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Myocardial infarction
|
1.4%
6/442 • Number of events 6
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Palpitations
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Pericardial effusion
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Pericarditis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.90%
4/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Endocrine disorders
Addison's disease
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 8
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Endocrine disorders
Goitre
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Endocrine disorders
Hypercalcaemia of malignancy
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Endocrine disorders
Inappropriate antidiuretic hormone secretion
|
0.45%
2/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Eye disorders
Diplopia
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.68%
3/442 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
1.4%
6/443 • Number of events 7
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Anal haemorrhage
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Constipation
|
1.1%
5/442 • Number of events 6
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.90%
4/443 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.90%
4/442 • Number of events 9
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
1.6%
7/443 • Number of events 9
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Diverticular perforation
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 6
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Duodenal ulcer haemorrhage
|
0.45%
2/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Duodenitis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Dysphagia
|
0.23%
1/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Faecaloma
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Gastritis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.68%
3/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
1.1%
5/443 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Gastrointestinal perforation
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Haematemesis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Ileus
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Ileus paralytic
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.45%
2/442 • Number of events 7
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Nausea
|
2.0%
9/442 • Number of events 17
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
2.5%
11/443 • Number of events 21
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Oesophageal obstruction
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Oesophagitis
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Peptic ulcer
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.45%
2/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.45%
2/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Small intestinal perforation
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.68%
3/442 • Number of events 6
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Vomiting
|
2.9%
13/442 • Number of events 20
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
2.5%
11/443 • Number of events 12
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Asthenia
|
0.45%
2/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
2.0%
9/443 • Number of events 15
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Chest pain
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Death
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Device dislocation
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Device malfunction
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Fatigue
|
0.23%
1/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Hypothermia
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Impaired healing
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 7
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Malaise
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Mucosal inflammation
|
0.45%
2/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Multi-organ failure
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Non-cardiac chest pain
|
1.1%
5/442 • Number of events 6
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Pain
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Pyrexia
|
0.68%
3/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.90%
4/443 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Hepatobiliary disorders
Acute hepatic failure
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Hepatobiliary disorders
Hepatic haemorrhage
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Immune system disorders
Hypersensitivity
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Appendicitis perforated
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Bacteraemia
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Bronchitis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Cellulitis
|
0.68%
3/442 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Clostridial infection
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Clostridium colitis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Clostridium difficile colitis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Device related sepsis
|
0.45%
2/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Diverticulitis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 8
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Empyema
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Enterobacter sepsis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Gastroenteritis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Hepatitis c
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Infection
|
0.45%
2/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Infectious peritonitis
|
0.45%
2/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Liver abscess
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Lobar pneumonia
|
0.45%
2/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Lung infection pseudomonal
|
0.23%
1/442 • Number of events 7
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Meningitis herpes
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Osteomyelitis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Perirectal abscess
|
0.23%
1/442 • Number of events 10
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Pneumonia
|
6.3%
28/442 • Number of events 39
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
6.1%
27/443 • Number of events 42
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Pneumonia pneumococcal
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Pneumonia streptococcal
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 17
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Pseudomonal sepsis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Respiratory tract infection
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Retroperitoneal abscess
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Sepsis
|
1.4%
6/442 • Number of events 7
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Sepsis syndrome
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Septic shock
|
0.45%
2/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Staphylococcal sepsis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Streptococcal bacteraemia
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Tooth abscess
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Urinary tract infection bacterial
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Wound abscess
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Compression fracture
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Fall
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.45%
2/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Head injury
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Radiation oesophagitis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 14
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.45%
2/442 • Number of events 15
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Injury, poisoning and procedural complications
Wrong drug administered
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
Alanine aminotransferase increased
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
Aspartate aminotransferase increased
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
Aspiration pleural cavity
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
International normalised ratio increased
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
Platelet count decreased
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
Troponin i increased
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Dehydration
|
4.5%
20/442 • Number of events 27
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
4.7%
21/443 • Number of events 26
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.23%
1/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.45%
2/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.1%
5/442 • Number of events 8
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.68%
3/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
1.8%
8/443 • Number of events 9
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Lactic acidosis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Metabolic alkalosis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Starvation
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 11
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.45%
2/442 • Number of events 8
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.90%
4/443 • Number of events 9
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Fracture nonunion
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
|
0.45%
2/442 • Number of events 6
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 8
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic pain
|
0.68%
3/442 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neurilemmoma
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pericardial effusion malignant
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.43%
1/235 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.45%
2/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Ataxia
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Cerebral infarction
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Cerebral ischaemia
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Cerebrovascular accident
|
1.1%
5/442 • Number of events 9
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Convulsion
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Dizziness
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Haemorrhagic stroke
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Ischaemic cerebral infarction
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Lethargy
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Metabolic encephalopathy
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Nerve compression
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 7
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Parkinson's disease
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 11
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Somnolence
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Status epilepticus
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.45%
2/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Syncope
|
0.68%
3/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.68%
3/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Unresponsive to stimuli
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Psychiatric disorders
Confusional state
|
1.1%
5/442 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Psychiatric disorders
Delirium
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Psychiatric disorders
Mental status changes
|
0.90%
4/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.23%
1/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Renal and urinary disorders
Renal failure
|
0.23%
1/442 • Number of events 7
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Renal and urinary disorders
Renal failure acute
|
1.6%
7/442 • Number of events 10
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.90%
4/443 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Renal and urinary disorders
Renal tubular necrosis
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Renal and urinary disorders
Urinary retention
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Acquired tracheo-oesophageal fistula
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.23%
1/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.23%
1/442 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial fistula
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.6%
7/442 • Number of events 30
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 22
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.6%
7/442 • Number of events 14
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
1.8%
8/443 • Number of events 18
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.4%
6/442 • Number of events 7
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.8%
8/442 • Number of events 11
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 6
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Hydropneumothorax
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.90%
4/443 • Number of events 10
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.68%
3/442 • Number of events 6
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
1.4%
6/443 • Number of events 9
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.45%
2/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.3%
10/442 • Number of events 21
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
2.0%
9/443 • Number of events 14
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.45%
2/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.5%
11/442 • Number of events 13
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.90%
4/443 • Number of events 4
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Surgical and medical procedures
Lung neoplasm surgery
|
0.23%
1/442 • Number of events 2
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Arterial thrombosis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Deep vein thrombosis
|
1.1%
5/442 • Number of events 16
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
3.2%
14/443 • Number of events 34
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Haemorrhage
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Hypertension
|
0.45%
2/442 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 7
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Hypotension
|
0.68%
3/442 • Number of events 3
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.68%
3/443 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Intra-abdominal haemorrhage
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Jugular vein thrombosis
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/442
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.23%
1/443 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Post thrombotic syndrome
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Shock
|
0.23%
1/442 • Number of events 1
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Superior vena cava syndrome
|
0.23%
1/442 • Number of events 5
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.00%
0/443
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
Other adverse events
| Measure |
Pem/Carbo/Bev
n=442 participants at risk
Induction:
Bevacizumab: Induction therapy 15 milligrams per kilogram (mg/kg) intravenously (IV) every 21 days for up to 4 cycles of 21 days Pemetrexed: Induction therapy 500 milligram per meter squared (mg/m\^2) IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days Carboplatin: Induction therapy of 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
Maintenance:
Pemetrexed: Maintenance therapy 500 mg/m\^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
|
Pac/Carbo/Bev
n=443 participants at risk
Induction:
Paclitaxel: Induction therapy 200 milligram per meter squared (mg/m ²) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days Bevacizumab: Induction therapy 15 mg/kg IV every 21 days for up to 4 cycles of 21 days Carboplatin: Induction therapy 6 area under the concentration curve (AUC 6) IV every 21 days for up to 4 cycles of 21 days
Maintenance:
Bevacizumab: Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.4%
46/442 • Number of events 272
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
24.2%
107/443 • Number of events 967
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.6%
60/442 • Number of events 299
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
14.4%
64/443 • Number of events 441
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Anaemia
|
40.0%
177/442 • Number of events 1367
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
30.7%
136/443 • Number of events 793
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Leukopenia
|
16.5%
73/442 • Number of events 387
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
17.2%
76/443 • Number of events 362
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Neutropenia
|
38.5%
170/442 • Number of events 733
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
49.4%
219/443 • Number of events 790
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
36.0%
159/442 • Number of events 829
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
23.7%
105/443 • Number of events 452
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Eye disorders
Lacrimation increased
|
7.0%
31/442 • Number of events 405
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
0.45%
2/443 • Number of events 12
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Abdominal pain
|
9.5%
42/442 • Number of events 171
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
8.8%
39/443 • Number of events 113
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Constipation
|
41.0%
181/442 • Number of events 1380
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
37.5%
166/443 • Number of events 931
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Diarrhoea
|
22.6%
100/442 • Number of events 536
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
26.6%
118/443 • Number of events 338
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Dyspepsia
|
11.1%
49/442 • Number of events 419
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
6.8%
30/443 • Number of events 155
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.7%
25/442 • Number of events 249
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
5.0%
22/443 • Number of events 178
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Nausea
|
53.4%
236/442 • Number of events 1465
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
50.3%
223/443 • Number of events 1157
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Stomatitis
|
13.8%
61/442 • Number of events 321
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
9.9%
44/443 • Number of events 159
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Gastrointestinal disorders
Vomiting
|
25.8%
114/442 • Number of events 369
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
24.4%
108/443 • Number of events 310
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Asthenia
|
9.0%
40/442 • Number of events 230
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
6.5%
29/443 • Number of events 178
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Fatigue
|
60.6%
268/442 • Number of events 2793
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
58.0%
257/443 • Number of events 2273
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Mucosal inflammation
|
11.5%
51/442 • Number of events 229
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
7.9%
35/443 • Number of events 110
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Oedema peripheral
|
14.9%
66/442 • Number of events 466
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
9.0%
40/443 • Number of events 249
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Pain
|
5.0%
22/442 • Number of events 87
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
7.0%
31/443 • Number of events 196
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
General disorders
Pyrexia
|
7.9%
35/442 • Number of events 104
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
9.5%
42/443 • Number of events 57
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Sinusitis
|
7.5%
33/442 • Number of events 111
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
4.3%
19/443 • Number of events 53
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.2%
32/442 • Number of events 103
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
5.9%
26/443 • Number of events 53
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Infections and infestations
Urinary tract infection
|
7.2%
32/442 • Number of events 84
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
9.5%
42/443 • Number of events 108
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
Alanine aminotransferase increased
|
8.4%
37/442 • Number of events 291
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
2.7%
12/443 • Number of events 47
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
Aspartate aminotransferase increased
|
7.5%
33/442 • Number of events 207
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
3.8%
17/443 • Number of events 52
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
Blood creatinine increased
|
5.7%
25/442 • Number of events 163
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
2.9%
13/443 • Number of events 29
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
Haemoglobin decreased
|
8.8%
39/442 • Number of events 322
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
5.0%
22/443 • Number of events 102
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
Platelet count decreased
|
6.6%
29/442 • Number of events 106
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
3.2%
14/443 • Number of events 39
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Investigations
Weight decreased
|
17.4%
77/442 • Number of events 464
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
15.3%
68/443 • Number of events 470
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
30.1%
133/442 • Number of events 865
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
32.7%
145/443 • Number of events 912
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Dehydration
|
15.4%
68/442 • Number of events 194
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
12.2%
54/443 • Number of events 155
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
8.6%
38/442 • Number of events 251
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
10.2%
45/443 • Number of events 236
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
6.3%
28/442 • Number of events 70
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
7.4%
33/443 • Number of events 76
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
7.7%
34/442 • Number of events 169
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
6.8%
30/443 • Number of events 186
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
3.6%
16/442 • Number of events 83
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
7.4%
33/443 • Number of events 204
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
7.5%
33/442 • Number of events 197
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
4.7%
21/443 • Number of events 141
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
9.5%
42/442 • Number of events 273
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
7.0%
31/443 • Number of events 246
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.7%
25/442 • Number of events 150
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
13.5%
60/443 • Number of events 394
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.7%
25/442 • Number of events 200
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
9.9%
44/443 • Number of events 413
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Dizziness
|
17.4%
77/442 • Number of events 404
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
14.2%
63/443 • Number of events 298
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Dysgeusia
|
15.2%
67/442 • Number of events 551
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
10.6%
47/443 • Number of events 283
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Headache
|
18.6%
82/442 • Number of events 516
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
15.1%
67/443 • Number of events 343
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Neuropathy peripheral
|
9.5%
42/442 • Number of events 413
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
32.7%
145/443 • Number of events 1394
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Paraesthesia
|
2.5%
11/442 • Number of events 85
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
5.4%
24/443 • Number of events 255
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
4.3%
19/442 • Number of events 218
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
16.5%
73/443 • Number of events 888
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Psychiatric disorders
Anxiety
|
11.8%
52/442 • Number of events 407
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
9.9%
44/443 • Number of events 379
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Psychiatric disorders
Confusional state
|
4.3%
19/442 • Number of events 95
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
5.2%
23/443 • Number of events 48
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Psychiatric disorders
Depression
|
11.8%
52/442 • Number of events 402
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
10.6%
47/443 • Number of events 414
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Psychiatric disorders
Insomnia
|
15.6%
69/442 • Number of events 535
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
19.6%
87/443 • Number of events 719
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Renal and urinary disorders
Proteinuria
|
14.3%
63/442 • Number of events 435
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
12.2%
54/443 • Number of events 449
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.6%
91/442 • Number of events 549
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
19.4%
86/443 • Number of events 568
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
7.2%
32/442 • Number of events 257
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
3.8%
17/443 • Number of events 126
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
19.9%
88/442 • Number of events 558
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
19.2%
85/443 • Number of events 503
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
26.5%
117/442 • Number of events 800
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
22.1%
98/443 • Number of events 599
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
9.3%
41/442 • Number of events 140
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
7.4%
33/443 • Number of events 115
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.6%
29/442 • Number of events 205
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
4.3%
19/443 • Number of events 153
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.7%
34/442 • Number of events 445
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
43.6%
193/443 • Number of events 2024
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.4%
15/442 • Number of events 72
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
6.8%
30/443 • Number of events 91
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.5%
42/442 • Number of events 239
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
12.6%
56/443 • Number of events 177
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
|
Vascular disorders
Hypertension
|
16.7%
74/442 • Number of events 800
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
15.8%
70/443 • Number of events 678
Deaths due to progressive disease are not considered adverse events and reported in the participant flow. All randomized participants who received at least 1 dose of study drug during the specified treatment phase.
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60