Trial Outcomes & Findings for Study of Cabozantinib (XL184) in Adults With Advanced Malignancies (NCT NCT00940225)
NCT ID: NCT00940225
Last Updated: 2024-04-25
Results Overview
Objective response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.0 per investigator The analysis of ORR in the RDT Cohorts were defined as the proportion of subjects with a best overall response of confirmed complete response (CR) or partial response (PR) per mRECIST 1.0 during the 12-week Lead-In Stage. In the NRE Ovarian Cohort, mRECIST 1.1 was used. ORR for the NRE CRPC Cohorts was not a primary objective and is therefore not captured in the table below.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
730 participants
Primary outcome timeframe
From initial dose through final study visit up to 44 months
Results posted on
2024-04-25
Participant Flow
Participant milestones
| Measure |
RDT Cohort - Castration-Resistant Prostate Cancer (CRPC)
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - Melanoma
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - Non-Small Cell Lung Cancer (NSCLC)
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - Pancreatic Cancer
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - Gastric/Gastroesophageal Junction Cancer (GEJ)
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - Hepatocellular Carcinoma (HCC)
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - Small Cell Lung Cancer (SCLC)
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - Ovarian Cancer
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - Metastatic Breast Cancer (MBC)
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
NRE Cohort - CRPC 100 mg
Subjects received a single oral daily dose of cabozantinib at 100 mg.
|
NRE Cohort - CRPC 39.4 mg
Subjects received a single oral daily dose of cabozantinib at 39.4 mg.
|
NRE Cohort - Ovarian Cancer 100mg
Subjects received a single oral daily dose of cabozantinib at 100 mg.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
171
|
77
|
60
|
20
|
21
|
41
|
21
|
70
|
45
|
93
|
51
|
60
|
|
Overall Study
COMPLETED
|
156
|
66
|
47
|
16
|
19
|
36
|
20
|
60
|
41
|
87
|
48
|
54
|
|
Overall Study
NOT COMPLETED
|
15
|
11
|
13
|
4
|
2
|
5
|
1
|
10
|
4
|
6
|
3
|
6
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of Cabozantinib (XL184) in Adults With Advanced Malignancies
Baseline characteristics by cohort
| Measure |
RDT Cohort - CRPC
n=171 Participants
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - Melanoma
n=77 Participants
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - NSCLC
n=60 Participants
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - Pancreatic Cancer
n=20 Participants
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - GEJ
n=21 Participants
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - HCC
n=41 Participants
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - SCLC
n=21 Participants
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - Ovarian Cancer
n=70 Participants
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
RDT Cohort - MBC
n=45 Participants
Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).
|
NRE Cohort - CRPC 100 mg
n=93 Participants
Subjects received a single oral daily dose of cabozantinib at 100 mg.
|
NRE Cohort - CRPC 39.4 mg
n=51 Participants
subjects received a single oral daily dose of cabozantinib at 39.4 mg.
|
NRE Cohort - Ovarian Cancer 100mg
n=60 Participants
subjects received a single oral daily dose of cabozantinib at 100 mg.
|
Total
n=730 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Customized
<= 40 years
|
0 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
4 Participants
n=24 Participants
|
6 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
23 Participants
n=36 Participants
|
|
Age, Customized
> 40 - <= 50 years
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
12 Participants
n=24 Participants
|
7 Participants
n=42 Participants
|
3 Participants
n=42 Participants
|
5 Participants
n=42 Participants
|
10 Participants
n=42 Participants
|
59 Participants
n=36 Participants
|
|
Age, Customized
> 50 - <= 65 years
|
60 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
22 Participants
n=8 Participants
|
12 Participants
n=8 Participants
|
32 Participants
n=24 Participants
|
26 Participants
n=42 Participants
|
41 Participants
n=42 Participants
|
24 Participants
n=42 Participants
|
33 Participants
n=42 Participants
|
321 Participants
n=36 Participants
|
|
Age, Customized
> 65 years
|
107 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
12 Participants
n=8 Participants
|
7 Participants
n=8 Participants
|
22 Participants
n=24 Participants
|
6 Participants
n=42 Participants
|
49 Participants
n=42 Participants
|
22 Participants
n=42 Participants
|
16 Participants
n=42 Participants
|
327 Participants
n=36 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
10 Participants
n=8 Participants
|
12 Participants
n=8 Participants
|
70 Participants
n=24 Participants
|
44 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
60 Participants
n=42 Participants
|
270 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
171 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
31 Participants
n=8 Participants
|
9 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
93 Participants
n=42 Participants
|
51 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
460 Participants
n=36 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Asian
|
12 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
15 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
40 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
35 Participants
n=36 Participants
|
|
Race (NIH/OMB)
White
|
145 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
22 Participants
n=8 Participants
|
18 Participants
n=8 Participants
|
66 Participants
n=24 Participants
|
41 Participants
n=42 Participants
|
85 Participants
n=42 Participants
|
45 Participants
n=42 Participants
|
51 Participants
n=42 Participants
|
633 Participants
n=36 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
3 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
9 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
1 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
3 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
12 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: From initial dose through final study visit up to 44 monthsObjective response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.0 per investigator The analysis of ORR in the RDT Cohorts were defined as the proportion of subjects with a best overall response of confirmed complete response (CR) or partial response (PR) per mRECIST 1.0 during the 12-week Lead-In Stage. In the NRE Ovarian Cohort, mRECIST 1.1 was used. ORR for the NRE CRPC Cohorts was not a primary objective and is therefore not captured in the table below.
Outcome measures
| Measure |
Lead-in Stage - CRPC
n=171 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Melanoma
n=77 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NSCLC
n=60 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Pancreatic Cancer
n=20 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Gastric/GEJ
n=21 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Hepatocellular Carcinoma
n=41 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - SCLC
n=21 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Ovarian Cancer
n=70 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Metastatic Breast Cancer
n=45 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NRE Ovarian Cancer
n=60 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Randomized Phase - HCC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - HCC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Objective Response Rate (ORR) - LEAD IN STAGE, RDT Cohorts and NRE Ovarian Cohort Only
|
4.7 percentage of participants
Interval 2.0 to 8.7
|
5.2 percentage of participants
Interval 1.8 to 12.4
|
10 percentage of participants
Interval 4.4 to 20.3
|
0 percentage of participants
Interval 0.0 to 15.4
|
4.8 percentage of participants
Interval 0.2 to 21.8
|
4.9 percentage of participants
Interval 0.9 to 16.1
|
4.8 percentage of participants
Interval 0.2 to 21.8
|
21.7 percentage of participants
Interval 13.1 to 32.4
|
13.6 percentage of participants
Interval 6.0 to 25.7
|
10.0 percentage of participants
Interval 3.3 to 21.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From initial dose through final study visit up to 15 monthsThe reduction of bone scan lesion area (BSLA) by \> 30% was used as the quantitative measure of BSR. BSR was a primary outcome measure for only the NRE CRPC Cohorts.
Outcome measures
| Measure |
Lead-in Stage - CRPC
n=93 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Melanoma
n=51 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NSCLC
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Pancreatic Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Gastric/GEJ
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Hepatocellular Carcinoma
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - SCLC
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Ovarian Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Metastatic Breast Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NRE Ovarian Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Randomized Phase - HCC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - HCC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Bone Scan Response (BSR) - NRE, CRPC
|
74.2 percentage of participants
Interval 64.1 to 82.7
|
47.1 percentage of participants
Interval 32.9 to 61.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From initial dose through final study visit up to 44 monthsProgression Free Survival during the Randomized Stage (Randomized Population)
Outcome measures
| Measure |
Lead-in Stage - CRPC
n=14 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Melanoma
n=17 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NSCLC
n=13 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Pancreatic Cancer
n=13 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Gastric/GEJ
n=8 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Hepatocellular Carcinoma
n=8 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - SCLC
n=3 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Ovarian Cancer
n=3 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Metastatic Breast Cancer
n=3 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NRE Ovarian Cancer
n=2 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Randomized Phase - HCC, Cabozantinib Arm
n=10 Participants
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - HCC, Placebo Arm
n=12 Participants
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Cabozantinib Arm
n=8 Participants
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Placebo Arm
n=2 Participants
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Cabozantinib Arm
n=7 Participants
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Placebo Arm
n=6 Participants
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Cabozantinib Arm
n=5 Participants
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Placebo Arm
n=5 Participants
placebo, 100 mg, po QD, ongoing until progression
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Progression-Free Survival (PFS) - Randomized Stage, RDT Cohorts Only
|
5.5 months
Interval 4.0 to 8.5
|
1.4 months
Interval 1.25 to 2.73
|
4.5 months
Interval 1.8 to 15.4
|
2.8 months
Interval 1.45 to 5.45
|
2.4 months
Interval 1.3 to 2.9
|
2.4 months
Interval 1.4 to 2.7
|
2.8 months
Interval 1.5 to 2.8
|
.07 months
Interval 0.07 to 0.07
|
NA months
Interval 2.3 to
There was only one out of three subjects evaluated; unable to estimate due to insufficient number of patients within cohort.
|
1.0 months
Interval 0.72 to 1.38
|
2.5 months
Interval 1.3 to 6.8
|
1.4 months
Interval 1.3 to 4.2
|
5.5 months
Interval 1.9 to 6.9
|
1.5 months
Interval 0.85 to 2.23
|
4.9 months
Interval 3.9 to 13.6
|
1.4 months
Interval 1.3 to 1.6
|
6.9 months
Interval 5.1 to 13.5
|
1.1 months
Interval 0.7 to 1.3
|
SECONDARY outcome
Timeframe: From initial dose through final study visit up to 44 monthsDuration of objective response was defined as the time from the tumor assessment that first documented PR or CR that was subsequently confirmed at least 28 days later until the date of documented progression. There were either few or no responders in the Gastric/GEJ, SCLC, and pancreatic cohorts so these cohorts are excluded.
Outcome measures
| Measure |
Lead-in Stage - CRPC
n=15 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Melanoma
n=6 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NSCLC
n=6 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Pancreatic Cancer
n=3 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Gastric/GEJ
n=15 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Hepatocellular Carcinoma
n=6 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - SCLC
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Ovarian Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Metastatic Breast Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NRE Ovarian Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Randomized Phase - HCC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - HCC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Objective Response (OR) - Responders From Lead-in Stage
|
5.59 Months
Interval 4.27 to 8.34
|
5.55 Months
Interval 2.99 to 13.86
|
6.90 Months
Interval 5.29 to 10.74
|
4.21 Months
Interval 2.99 to
Unable to estimate due to low numbers.
|
11.24 Months
Interval 7.2 to
Unable to estimate due to low numbers.
|
3.29 Months
Interval 2.79 to 4.21
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From initial dose through final study visit up to 44 monthsProgression-free survival (PFS) from first dose throughout the study was estimated for all subjects (safety population) using a piecewise method.
Outcome measures
| Measure |
Lead-in Stage - CRPC
n=171 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Melanoma
n=77 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NSCLC
n=60 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Pancreatic Cancer
n=20 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Gastric/GEJ
n=21 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Hepatocellular Carcinoma
n=41 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - SCLC
n=21 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Ovarian Cancer
n=70 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Metastatic Breast Cancer
n=45 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NRE Ovarian Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Randomized Phase - HCC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - HCC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Progression Free Survival (PFS) - Throughout the Study
|
6.8 months
Interval 3.9 to 9.7
|
2.8 months
Interval 1.4 to 6.9
|
4.0 months
Interval 1.4 to 5.7
|
2.7 months
Interval 1.3 to 5.5
|
1.4 months
Interval 1.3 to
Unable to estimate as number of events is too low.
|
5.2 months
Interval 3.6 to 9.3
|
3.4 months
Interval 1.4 to 8.2
|
5.5 months
Interval 2.7 to 11.0
|
4.3 months
Interval 1.4 to 8.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From initial dose through final study visit up to 15 monthsThe duration of BSR per IRF was calculated for CRPC subjects with an objective response (CR or PR) during the study.
Outcome measures
| Measure |
Lead-in Stage - CRPC
n=69 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Melanoma
n=24 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NSCLC
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Pancreatic Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Gastric/GEJ
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Hepatocellular Carcinoma
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - SCLC
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Ovarian Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Metastatic Breast Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NRE Ovarian Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Randomized Phase - HCC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - HCC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Bone Scan Response - NRE Cohorts, CRPC Only
|
5.2 months
Interval 4.07 to 6.67
|
NA months
Unable to Estimate due to low numbers.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From initial dose through final study visit up to 15 monthsOutcome measures
| Measure |
Lead-in Stage - CRPC
n=93 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Melanoma
n=51 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NSCLC
n=60 Participants
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Pancreatic Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Gastric/GEJ
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Hepatocellular Carcinoma
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - SCLC
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Ovarian Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - Metastatic Breast Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Lead-in Stage - NRE Ovarian Cancer
cabozantinib, 100 mg, po QD for 12 weeks
|
Randomized Phase - HCC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - HCC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - SCLC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - Ovarian Cancer, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Cabozantinib Arm
cabozantinib, 100 mg, po QD, ongoing until progression
|
Randomized Phase - MBC, Placebo Arm
placebo, 100 mg, po QD, ongoing until progression
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Survival (OS) - NRE Cohorts, CRPC and Ovarian Only
|
11.1 months
Interval 9.17 to 13.34
|
8.0 months
Interval 7.92 to
Unable to Estimate due to low numbers.
|
8.5 months
Interval 5.88 to 11.73
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
RDT All Cohorts
Serious events: 223 serious events
Other events: 524 other events
Deaths: 54 deaths
NRE Cohort - CRPC 100mg (Castration-Resistant Prostate Cancer)
Serious events: 53 serious events
Other events: 93 other events
Deaths: 53 deaths
NRE Cohort - CRPC 39.4mg (Castration-Resistant Prostate Cancer)
Serious events: 30 serious events
Other events: 50 other events
Deaths: 13 deaths
NRE Cohort - Ovarian 100mg
Serious events: 34 serious events
Other events: 59 other events
Deaths: 33 deaths
Serious adverse events
| Measure |
RDT All Cohorts
n=526 participants at risk
Includes all tumor types from the 203 RDT cohort: castration-resistant prostate cancer (CRPC), melanoma, non-small cell lung cancer (NSCLC), pancreatic cancer, gastric/gastroesophageal junction (GEJ) cancer, hepatocellular carcinoma (HCC), small cell lung cancer (SCLC), ovarian cancer, and metastatic breast cancer
|
NRE Cohort - CRPC 100mg (Castration-Resistant Prostate Cancer)
n=93 participants at risk
Subjects received a single oral daily dose of cabozantinib at 100 mg.
|
NRE Cohort - CRPC 39.4mg (Castration-Resistant Prostate Cancer)
n=51 participants at risk
Subjects received a single oral daily dose of cabozantinib at 39.4 mg.
|
NRE Cohort - Ovarian 100mg
n=60 participants at risk
Subjects received a single oral daily dose of cabozantinib at 100 mg.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.5%
8/526
|
4.3%
4/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.19%
1/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.76%
4/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Cardiac disorders
Angina Pectoris
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Cardiac disorders
Atrial Fibrillation
|
0.38%
2/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Cardiac disorders
Atrioventricular Block
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Cardiac disorders
Cardiac Arrest
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Cardiac disorders
Cardiac Failure Congestive
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Cardiac disorders
Cardiac Tamponade
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Cardiac disorders
Coronary Artery Stenosis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Cardiac disorders
Palpitations
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Cardiac disorders
Pericardial Effusion
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Cardiac disorders
Supraventricular Tachycardia
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Cardiac disorders
Tachycardia
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Ear and labyrinth disorders
Vertigo
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Endocrine disorders
Adrenal Insufficiency
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Endocrine disorders
Hypopituitarism
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Abdominal Distension
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Abdominal Pain
|
1.7%
9/526
|
2.2%
2/93
|
3.9%
2/51
|
11.7%
7/60
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Anal Fissure
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Anal Ulcer
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Ascites
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Gastrointestinal disorders
Constipation
|
0.76%
4/526
|
1.1%
1/93
|
0.00%
0/51
|
5.0%
3/60
|
|
Gastrointestinal disorders
Diarrhoea
|
2.9%
15/526
|
2.2%
2/93
|
0.00%
0/51
|
5.0%
3/60
|
|
Gastrointestinal disorders
Diverticular Perforation
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Duodenal Ulcer Haemorrhage
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Dyspepsia
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Enterocutaneous Fistula
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Gastrointestinal Haemorrhage
|
0.95%
5/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Gastroesophageal Reflux Disease
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Haematemesis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Inflammatory Bowel Disease
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Inguinal Hernia
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
0.57%
3/526
|
0.00%
0/93
|
0.00%
0/51
|
6.7%
4/60
|
|
Gastrointestinal disorders
Intestinal Perforation
|
0.76%
4/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Lower Gastrointestinal Haemorrhage
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Melaena
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Nausea
|
2.3%
12/526
|
9.7%
9/93
|
0.00%
0/51
|
13.3%
8/60
|
|
Gastrointestinal disorders
Obstruction Gastric
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Oesophagitis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Pancreatitis
|
0.38%
2/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Pancreatitis Acute
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Peritoneal Hemorrhage
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Pneumoperitoneum
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Proctalgia
|
0.19%
1/526
|
1.1%
1/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Gastrointestinal disorders
Rectal Haemorrhage
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Rectal Obstruction
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Rectal Perforation
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Rectal Stenosis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Small Intestinal Obstruction
|
0.95%
5/526
|
0.00%
0/93
|
0.00%
0/51
|
8.3%
5/60
|
|
Gastrointestinal disorders
Vomiting
|
2.9%
15/526
|
7.5%
7/93
|
0.00%
0/51
|
18.3%
11/60
|
|
General disorders
Asthenia
|
1.7%
9/526
|
1.1%
1/93
|
2.0%
1/51
|
0.00%
0/60
|
|
General disorders
Chest Pain
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
General disorders
Death
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
General disorders
Drug Withdrawal Syndrome
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
General disorders
Fatigue
|
0.38%
2/526
|
5.4%
5/93
|
2.0%
1/51
|
1.7%
1/60
|
|
General disorders
General Physical Health Deterioration
|
0.95%
5/526
|
0.00%
0/93
|
0.00%
0/51
|
5.0%
3/60
|
|
General disorders
Malaise
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
General disorders
Multi-Organ Failure
|
0.76%
4/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
General disorders
Non-Cardiac Chest Pain
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
General disorders
Oedema Peripheral
|
0.57%
3/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
General disorders
Pain
|
0.38%
2/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
General disorders
Pyrexia
|
0.95%
5/526
|
2.2%
2/93
|
0.00%
0/51
|
6.7%
4/60
|
|
General disorders
Acute Hepatic Failure
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Hepatobiliary disorders
Bile Duct Obstruction
|
0.19%
1/526
|
0.00%
0/93
|
3.9%
2/51
|
0.00%
0/60
|
|
Hepatobiliary disorders
Cholangitis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Hepatobiliary disorders
Cholecystitis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Hepatobiliary disorders
Cholestasis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Hepatobiliary disorders
Hepatic Failure
|
0.95%
5/526
|
1.1%
1/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Hepatobiliary disorders
Jaundice Cholestatic
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Hepatobiliary disorders
Portal Vein Thrombosis
|
0.19%
1/526
|
2.2%
2/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Immune system disorders
Anaphylactic Reaction
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Immune system disorders
Drug Hypersensitivity
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Abscess Limb
|
0.19%
1/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Bronchitis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Infections and infestations
Clostridium Difficile Colitis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Clostridium Difficile Infection
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Cystitis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Device Related Infection
|
0.19%
1/526
|
1.1%
1/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Infections and infestations
Diverticulitis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Douglas' Abscess
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Empyema
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Escherichia Bacteremia
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Gastroenteritis Viral
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Herpes Oesophagitis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Klebsiella Bacteraemia
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Otitis Media
|
0.19%
1/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Pelvic Abscess
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Perirectal Abscess
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Peritonitis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Pneumonia
|
3.0%
16/526
|
3.2%
3/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Infections and infestations
Rectal Abscess
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Sepsis
|
0.95%
5/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Septic Shock
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Infections and infestations
Staphylococcal Infection
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Staphylococcal Sepsis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Urinary Tract Infection
|
1.3%
7/526
|
5.4%
5/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Urosepsis
|
0.19%
1/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Infections and infestations
Wound Infection
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Wound Sepsis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Hip Fracture
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Laceration
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Radiation Pneumonitis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Rib Fracture
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Subdural Haematoma
|
0.19%
1/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Wound Dehiscence
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Investigations
Amylase Increased
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Investigations
Aspartate Aminotransferase Increased
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Investigations
Blood Uric Acid Increased
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Investigations
Lipase Increased
|
0.19%
1/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
0.38%
2/526
|
0.00%
0/93
|
2.0%
1/51
|
3.3%
2/60
|
|
Metabolism and nutrition disorders
Dehydration
|
3.2%
17/526
|
6.5%
6/93
|
3.9%
2/51
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Diabetic Ketoacidosis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Failure to Thrive
|
0.57%
3/526
|
2.2%
2/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Gout
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.95%
5/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.57%
3/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.3%
7/526
|
2.2%
2/93
|
0.00%
0/51
|
3.3%
2/60
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.95%
5/526
|
5.4%
5/93
|
7.8%
4/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Flank Pain
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Muscle Haemorrhage
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
0.00%
0/526
|
1.1%
1/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis of Jaw
|
0.19%
1/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
0.19%
1/526
|
2.2%
2/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Pathological Fracture
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial Tumor Haemorrhage
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Melanoma
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Pleural Effusion
|
0.76%
4/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Central Nervous System
|
0.19%
1/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic Pain
|
0.38%
2/526
|
1.1%
1/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Small Cell Lung Cancer
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous Cell Carcinoma of the Oral Cavity
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Cerebral Haemorrhage
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Cerebrovascular Accident
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Convulsion
|
0.57%
3/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Nervous system disorders
Dizziness
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Encephalopathy
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Headache
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Hepatic Encephalopathy
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Occipital Neuralgia
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Presyncope
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Speech Disorder
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Spinal Cord Compression
|
0.19%
1/526
|
1.1%
1/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Nervous system disorders
Subdural Effusion
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Syncope
|
0.57%
3/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Nervous system disorders
Transient Ischaemic Attack
|
0.57%
3/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
VIth Nerve Paralysis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Psychiatric disorders
Confusional State
|
1.1%
6/526
|
2.2%
2/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Psychiatric disorders
Mental Status Change
|
1.7%
9/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Renal and urinary disorders
Acute Prerenal Failure
|
0.38%
2/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Renal and urinary disorders
Haematuria
|
0.57%
3/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Renal and urinary disorders
Haemorrhage Urinary Tract
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Renal and urinary disorders
Hydronephrosis
|
0.57%
3/526
|
1.1%
1/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Renal and urinary disorders
Renal Failure
|
0.95%
5/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Renal and urinary disorders
Renal Failure Acute
|
2.1%
11/526
|
4.3%
4/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Renal and urinary disorders
Ureteric Obstruction
|
0.19%
1/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Renal and urinary disorders
Urethral Obstruction
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Renal and urinary disorders
Urinary Tract Obstruction
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.5%
8/526
|
4.3%
4/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.19%
1/526
|
2.2%
2/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
1.1%
6/526
|
1.1%
1/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.38%
2/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.57%
3/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
4.4%
23/526
|
7.5%
7/93
|
15.7%
8/51
|
1.7%
1/60
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Thrombosis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
1.3%
7/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Skin and subcutaneous tissue disorders
Decubitus Ulcer
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Skin and subcutaneous tissue disorders
Rash Pruritic
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Deep Vein Thrombosis
|
2.3%
12/526
|
1.1%
1/93
|
3.9%
2/51
|
0.00%
0/60
|
|
Vascular disorders
Haemorrhage
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Hypertension
|
0.57%
3/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Hypotension
|
0.95%
5/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Hypovolaemic Shock
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Lymphoedema
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Orthostatic Hypotension
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Pelvic Venous Thrombosis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Venous Stenosis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Venous Thrombosis
|
0.19%
1/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Blood and lymphatic system disorders
Disseminated Intravascular Coagulation
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Blood and lymphatic system disorders
Idiopathic Thrombocytopenic Purpura
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Cardiac disorders
Sinus Bradycardia
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Eye disorders
Cataract
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Eye disorders
Corneal Epithelium Defect
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Eye disorders
Macular Oedema
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Eye disorders
Parophthalmia
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Abdominal Hernia
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Gastrointestinal disorders
Anal Fistula
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/526
|
2.2%
2/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Enterovesical Fistula
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Gastric Ulcer
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Ileus Paralytic
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Gastrointestinal disorders
Retroperitoneal Hematoma
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Upper Gastrointestinal Hemorrhage
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
General disorders
Performance Status Decreased
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Infections and infestations
Bacterial Sepsis
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Infections and infestations
Cellulitis
|
0.00%
0/526
|
2.2%
2/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Diabetic Foot Infection
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Lung Infection
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Pneumonia Fungal
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Infections and infestations
Tooth Infection
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Clavicle Fracture
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Spinal Compression Fracture
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Injury, poisoning and procedural complications
Wrist Fracture
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Investigations
Alanine Aminotransferase Increased
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Investigations
Blood Sodium Decreased
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Investigations
Liver Function Test Abnormal
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Investigations
Platelet Count Decreased
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Investigations
Transaminases Increased
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
0.00%
0/526
|
6.5%
6/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Groin Pain
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian Cancer
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer
|
0.00%
0/526
|
3.2%
3/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Nervous system disorders
Depressed Level of Consciousness
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Nervous system disorders
Haemorrhage Intracranial
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Nervous system disorders
Sciatica
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Reproductive system and breast disorders
Vaginal Haemorrhage
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopleural Fistula
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Alveolar Hemorrhage
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Bleeding Varicose Vein
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Haematoma
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Vascular disorders
Venous Thrombosis Limb
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
1.7%
1/60
|
Other adverse events
| Measure |
RDT All Cohorts
n=526 participants at risk
Includes all tumor types from the 203 RDT cohort: castration-resistant prostate cancer (CRPC), melanoma, non-small cell lung cancer (NSCLC), pancreatic cancer, gastric/gastroesophageal junction (GEJ) cancer, hepatocellular carcinoma (HCC), small cell lung cancer (SCLC), ovarian cancer, and metastatic breast cancer
|
NRE Cohort - CRPC 100mg (Castration-Resistant Prostate Cancer)
n=93 participants at risk
Subjects received a single oral daily dose of cabozantinib at 100 mg.
|
NRE Cohort - CRPC 39.4mg (Castration-Resistant Prostate Cancer)
n=51 participants at risk
Subjects received a single oral daily dose of cabozantinib at 39.4 mg.
|
NRE Cohort - Ovarian 100mg
n=60 participants at risk
Subjects received a single oral daily dose of cabozantinib at 100 mg.
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
19.4%
102/526
|
31.2%
29/93
|
23.5%
12/51
|
18.3%
11/60
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.8%
36/526
|
7.5%
7/93
|
2.0%
1/51
|
11.7%
7/60
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
11.4%
60/526
|
3.2%
3/93
|
7.8%
4/51
|
18.3%
11/60
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
4.4%
23/526
|
7.5%
7/93
|
2.0%
1/51
|
5.0%
3/60
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.2%
43/526
|
1.1%
1/93
|
0.00%
0/51
|
13.3%
8/60
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
10.3%
54/526
|
6.5%
6/93
|
7.8%
4/51
|
11.7%
7/60
|
|
Skin and subcutaneous tissue disorders
Hair Colour Changes
|
10.1%
53/526
|
4.3%
4/93
|
0.00%
0/51
|
13.3%
8/60
|
|
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome
|
34.0%
179/526
|
25.8%
24/93
|
13.7%
7/51
|
33.3%
20/60
|
|
Skin and subcutaneous tissue disorders
Rash
|
19.4%
102/526
|
20.4%
19/93
|
11.8%
6/51
|
20.0%
12/60
|
|
Vascular disorders
Hypertension
|
24.0%
126/526
|
26.9%
25/93
|
19.6%
10/51
|
31.7%
19/60
|
|
Gastrointestinal disorders
Stomatitis
|
18.8%
99/526
|
16.1%
15/93
|
9.8%
5/51
|
28.3%
17/60
|
|
Gastrointestinal disorders
Vomiting
|
35.7%
188/526
|
40.9%
38/93
|
37.3%
19/51
|
41.7%
25/60
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
6.5%
34/526
|
22.6%
21/93
|
13.7%
7/51
|
3.3%
2/60
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.8%
36/526
|
9.7%
9/93
|
2.0%
1/51
|
6.7%
4/60
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
17.1%
90/526
|
31.2%
29/93
|
21.6%
11/51
|
15.0%
9/60
|
|
Nervous system disorders
Dizziness
|
16.3%
86/526
|
16.1%
15/93
|
13.7%
7/51
|
30.0%
18/60
|
|
Nervous system disorders
Dysgeusia
|
29.7%
156/526
|
37.6%
35/93
|
27.5%
14/51
|
35.0%
21/60
|
|
Nervous system disorders
Headache
|
15.0%
79/526
|
14.0%
13/93
|
15.7%
8/51
|
28.3%
17/60
|
|
Nervous system disorders
Neuropathy Peripheral
|
7.2%
38/526
|
7.5%
7/93
|
0.00%
0/51
|
10.0%
6/60
|
|
Psychiatric disorders
Anxiety
|
6.5%
34/526
|
2.2%
2/93
|
2.0%
1/51
|
13.3%
8/60
|
|
Psychiatric disorders
Confusional State
|
6.7%
35/526
|
7.5%
7/93
|
0.00%
0/51
|
3.3%
2/60
|
|
Psychiatric disorders
Depression
|
7.2%
38/526
|
4.3%
4/93
|
3.9%
2/51
|
6.7%
4/60
|
|
Psychiatric disorders
Insomnia
|
8.4%
44/526
|
7.5%
7/93
|
3.9%
2/51
|
6.7%
4/60
|
|
Renal and urinary disorders
Dysuria
|
5.1%
27/526
|
3.2%
3/93
|
7.8%
4/51
|
6.7%
4/60
|
|
Renal and urinary disorders
Proteinuria
|
6.5%
34/526
|
0.00%
0/93
|
0.00%
0/51
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
88/526
|
15.1%
14/93
|
5.9%
3/51
|
18.3%
11/60
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
27.0%
142/526
|
36.6%
34/93
|
17.6%
9/51
|
26.7%
16/60
|
|
General disorders
Asthenia
|
21.9%
115/526
|
19.4%
18/93
|
13.7%
7/51
|
16.7%
10/60
|
|
General disorders
Fatigue
|
65.6%
345/526
|
81.7%
76/93
|
62.7%
32/51
|
78.3%
47/60
|
|
General disorders
Mucosal Inflammation
|
16.0%
84/526
|
15.1%
14/93
|
15.7%
8/51
|
16.7%
10/60
|
|
General disorders
Oedema Peripheral
|
14.4%
76/526
|
14.0%
13/93
|
21.6%
11/51
|
11.7%
7/60
|
|
General disorders
Pain
|
6.8%
36/526
|
5.4%
5/93
|
11.8%
6/51
|
6.7%
4/60
|
|
General disorders
Pyrexia
|
8.9%
47/526
|
6.5%
6/93
|
2.0%
1/51
|
5.0%
3/60
|
|
Infections and infestations
Urinary Tract Infection
|
11.2%
59/526
|
5.4%
5/93
|
7.8%
4/51
|
18.3%
11/60
|
|
Investigations
Alanine Aminotransferase Increased
|
13.5%
71/526
|
7.5%
7/93
|
5.9%
3/51
|
26.7%
16/60
|
|
Investigations
Aspartate Aminotransferase Increased
|
17.9%
94/526
|
10.8%
10/93
|
9.8%
5/51
|
35.0%
21/60
|
|
Investigations
Lipase Increased
|
6.7%
35/526
|
2.2%
2/93
|
2.0%
1/51
|
5.0%
3/60
|
|
Investigations
Weight Decreased
|
31.4%
165/526
|
45.2%
42/93
|
37.3%
19/51
|
30.0%
18/60
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
51.3%
270/526
|
75.3%
70/93
|
43.1%
22/51
|
51.7%
31/60
|
|
Metabolism and nutrition disorders
Dehydration
|
14.1%
74/526
|
18.3%
17/93
|
5.9%
3/51
|
15.0%
9/60
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
11.8%
62/526
|
15.1%
14/93
|
11.8%
6/51
|
15.0%
9/60
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
13.3%
70/526
|
6.5%
6/93
|
5.9%
3/51
|
20.0%
12/60
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
4.8%
25/526
|
6.5%
6/93
|
5.9%
3/51
|
5.0%
3/60
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
7.8%
41/526
|
5.4%
5/93
|
5.9%
3/51
|
8.3%
5/60
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.4%
39/526
|
31.2%
29/93
|
11.8%
6/51
|
8.3%
5/60
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
14.1%
74/526
|
32.3%
30/93
|
21.6%
11/51
|
16.7%
10/60
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
10.6%
56/526
|
10.8%
10/93
|
17.6%
9/51
|
21.7%
13/60
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
5.1%
27/526
|
14.0%
13/93
|
5.9%
3/51
|
3.3%
2/60
|
|
Blood and lymphatic system disorders
Anaemia
|
12.0%
63/526
|
31.2%
29/93
|
9.8%
5/51
|
16.7%
10/60
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.1%
27/526
|
7.5%
7/93
|
5.9%
3/51
|
8.3%
5/60
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.7%
35/526
|
8.6%
8/93
|
5.9%
3/51
|
11.7%
7/60
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
11.0%
58/526
|
10.8%
10/93
|
5.9%
3/51
|
15.0%
9/60
|
|
Endocrine disorders
Hypothyroidism
|
12.5%
66/526
|
32.3%
30/93
|
7.8%
4/51
|
25.0%
15/60
|
|
Gastrointestinal disorders
Abdominal Distension
|
5.9%
31/526
|
4.3%
4/93
|
5.9%
3/51
|
16.7%
10/60
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
9.9%
52/526
|
6.5%
6/93
|
5.9%
3/51
|
11.7%
7/60
|
|
Gastrointestinal disorders
Constipation
|
31.9%
168/526
|
34.4%
32/93
|
31.4%
16/51
|
35.0%
21/60
|
|
Gastrointestinal disorders
Diarrhoea
|
59.7%
314/526
|
71.0%
66/93
|
45.1%
23/51
|
76.7%
46/60
|
|
Gastrointestinal disorders
Dry Mouth
|
16.5%
87/526
|
9.7%
9/93
|
7.8%
4/51
|
20.0%
12/60
|
|
Gastrointestinal disorders
Dyspepsia
|
12.0%
63/526
|
12.9%
12/93
|
13.7%
7/51
|
25.0%
15/60
|
|
Gastrointestinal disorders
Dysphagia
|
7.2%
38/526
|
5.4%
5/93
|
0.00%
0/51
|
13.3%
8/60
|
|
Gastrointestinal disorders
Flatulence
|
6.3%
33/526
|
8.6%
8/93
|
5.9%
3/51
|
8.3%
5/60
|
|
Gastrointestinal disorders
Gastrooesophageal Reflux Disease
|
8.6%
45/526
|
6.5%
6/93
|
9.8%
5/51
|
15.0%
9/60
|
|
Gastrointestinal disorders
Glossodynia
|
8.0%
42/526
|
2.2%
2/93
|
5.9%
3/51
|
3.3%
2/60
|
|
Gastrointestinal disorders
Nausea
|
51.1%
269/526
|
68.8%
64/93
|
58.8%
30/51
|
60.0%
36/60
|
|
Gastrointestinal disorders
Oral Pain
|
12.9%
68/526
|
11.8%
11/93
|
3.9%
2/51
|
6.7%
4/60
|
|
Gastrointestinal disorders
Abdominal Pain
|
22.8%
120/526
|
18.3%
17/93
|
15.7%
8/51
|
38.3%
23/60
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
0.00%
0/526
|
12.9%
12/93
|
11.8%
6/51
|
1.7%
1/60
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
0.00%
0/526
|
14.0%
13/93
|
11.8%
6/51
|
0.00%
0/60
|
|
Vascular disorders
Hypotension
|
0.00%
0/526
|
10.8%
10/93
|
3.9%
2/51
|
1.7%
1/60
|
|
Gastrointestinal disorders
Chest Pain
|
0.00%
0/526
|
8.6%
8/93
|
5.9%
3/51
|
3.3%
2/60
|
|
Vascular disorders
Pallor
|
0.00%
0/526
|
7.5%
7/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/526
|
5.4%
5/93
|
3.9%
2/51
|
1.7%
1/60
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/526
|
6.5%
6/93
|
3.9%
2/51
|
8.3%
5/60
|
|
Investigations
Platelet Count Decreased
|
0.00%
0/526
|
5.4%
5/93
|
0.00%
0/51
|
3.3%
2/60
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/526
|
6.5%
6/93
|
5.9%
3/51
|
0.00%
0/60
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/526
|
5.4%
5/93
|
2.0%
1/51
|
0.00%
0/60
|
|
General disorders
Chills
|
0.00%
0/526
|
5.4%
5/93
|
0.00%
0/51
|
8.3%
5/60
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea Exertional
|
0.00%
0/526
|
5.4%
5/93
|
5.9%
3/51
|
3.3%
2/60
|
|
Musculoskeletal and connective tissue disorders
Flank Pain
|
0.00%
0/526
|
5.4%
5/93
|
2.0%
1/51
|
0.00%
0/60
|
|
Investigations
Haemoglobin Decreased
|
0.00%
0/526
|
5.4%
5/93
|
3.9%
2/51
|
0.00%
0/60
|
|
Vascular disorders
Hot Flush
|
0.00%
0/526
|
5.4%
5/93
|
0.00%
0/51
|
3.3%
2/60
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
0.00%
0/526
|
5.4%
5/93
|
3.9%
2/51
|
3.3%
2/60
|
|
General disorders
Spinal Pain
|
0.00%
0/526
|
5.4%
5/93
|
3.9%
2/51
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/526
|
4.3%
4/93
|
5.9%
3/51
|
0.00%
0/60
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/526
|
4.3%
4/93
|
2.0%
1/51
|
5.0%
3/60
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/526
|
4.3%
4/93
|
5.9%
3/51
|
3.3%
2/60
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/526
|
3.2%
3/93
|
11.8%
6/51
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/526
|
3.2%
3/93
|
2.0%
1/51
|
16.7%
10/60
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/526
|
3.2%
3/93
|
9.8%
5/51
|
3.3%
2/60
|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
0.00%
0/526
|
3.2%
3/93
|
0.00%
0/51
|
6.7%
4/60
|
|
Investigations
Transaminases Increased
|
0.00%
0/526
|
3.2%
3/93
|
0.00%
0/51
|
5.0%
3/60
|
|
Renal and urinary disorders
Urinary Incontinence
|
0.00%
0/526
|
3.2%
3/93
|
7.8%
4/51
|
0.00%
0/60
|
|
Investigations
Blood Alkaline Phosphatase Increased
|
0.00%
0/526
|
2.2%
2/93
|
5.9%
3/51
|
18.3%
11/60
|
|
Investigations
Blood Creatinine Increased
|
0.00%
0/526
|
2.2%
2/93
|
5.9%
3/51
|
3.3%
2/60
|
|
Investigations
Gamma-Glutamyltransferase Increased
|
0.00%
0/526
|
2.2%
2/93
|
2.0%
1/51
|
11.7%
7/60
|
|
Musculoskeletal and connective tissue disorders
Groin Pain
|
0.00%
0/526
|
2.2%
2/93
|
5.9%
3/51
|
3.3%
2/60
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/526
|
2.2%
2/93
|
3.9%
2/51
|
5.0%
3/60
|
|
Nervous system disorders
Syncope
|
0.00%
0/526
|
2.2%
2/93
|
0.00%
0/51
|
5.0%
3/60
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/526
|
2.2%
2/93
|
2.0%
1/51
|
5.0%
3/60
|
|
Eye disorders
Vision Blurred
|
0.00%
0/526
|
2.2%
2/93
|
7.8%
4/51
|
3.3%
2/60
|
|
Investigations
Blood Thyroid Stimulating Hormone Increased
|
0.00%
0/526
|
1.1%
1/93
|
0.00%
0/51
|
6.7%
4/60
|
|
General disorders
Chest Discomfort
|
0.00%
0/526
|
1.1%
1/93
|
5.9%
3/51
|
5.0%
3/60
|
|
Nervous system disorders
Cognitive Disorder
|
0.00%
0/526
|
1.1%
1/93
|
3.9%
2/51
|
5.0%
3/60
|
|
Eye disorders
Dry Eye
|
0.00%
0/526
|
1.1%
1/93
|
2.0%
1/51
|
5.0%
3/60
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/526
|
1.1%
1/93
|
3.9%
2/51
|
5.0%
3/60
|
|
Gastrointestinal disorders
Hypoaesthesia Oral
|
0.00%
0/526
|
1.1%
1/93
|
5.9%
3/51
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/526
|
1.1%
1/93
|
2.0%
1/51
|
11.7%
7/60
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/526
|
1.1%
1/93
|
2.0%
1/51
|
6.7%
4/60
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/526
|
1.1%
1/93
|
2.0%
1/51
|
6.7%
4/60
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
6.7%
4/60
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
8.3%
5/60
|
|
Investigations
Blood Albumin Decreased
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
5.0%
3/60
|
|
Gastrointestinal disorders
Early Satiety
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
5.0%
3/60
|
|
Renal and urinary disorders
Micturition Urgency
|
0.00%
0/526
|
0.00%
0/93
|
5.9%
3/51
|
1.7%
1/60
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
8.3%
5/60
|
|
Psychiatric disorders
Sleep Disorder
|
0.00%
0/526
|
0.00%
0/93
|
0.00%
0/51
|
5.0%
3/60
|
|
Vascular disorders
Thrombosis
|
0.00%
0/526
|
0.00%
0/93
|
2.0%
1/51
|
5.0%
3/60
|
|
Nervous system disorders
Memory Impairment
|
0.00%
0/526
|
2.2%
2/93
|
0.00%
0/51
|
6.7%
4/60
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place