Trial Outcomes & Findings for Chemotherapy and Radiation in Treating Participants With Stage 3 Non-Small Cell Lung Cancer (NCT NCT00686959)

Last Updated: 2016-06-28

Results Overview

Overall survival (OS) time is from baseline to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the data cut-off date. OS was summarized using Kaplan-Meier estimates.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

598 participants

Primary outcome timeframe

Baseline to Date of Death from Any Cause (Up to 71.4 Months)

Results posted on

2016-06-28

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A: Pemetrexed + Cisplatin and TRT Participants were treated with Pemetrexed plus Cisplatin and concurrent thoracic radiation therapy (TRT) ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 milligrams per meter squared (mg/m\^2), intravenous (IV) on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gray \[Gy\] per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles	Arm B: Etoposide + Cisplatin and TRT Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m\^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m\^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m\^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22
Overall Study STARTED	301	297
Overall Study Received at Least One Dose of Study Drug	283	272
Overall Study Entered Consolidation Phase	229	202
Overall Study COMPLETED	177	180
Overall Study NOT COMPLETED	124	117

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Pemetrexed + Cisplatin and TRT Participants were treated with Pemetrexed plus Cisplatin and concurrent thoracic radiation therapy (TRT) ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 milligrams per meter squared (mg/m\^2), intravenous (IV) on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gray \[Gy\] per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles	Arm B: Etoposide + Cisplatin and TRT Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m\^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m\^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m\^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22
Overall Study Participants censored (no death events)	124	117

Baseline Characteristics

Chemotherapy and Radiation in Treating Participants With Stage 3 Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Pemetrexed + Cisplatin and TRT n=301 Participants Participants were treated with Pemetrexed plus Cisplatin and concurrent TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gy per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles	Arm B: Etoposide + Cisplatin and TRT n=297 Participants Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m\^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m\^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m\^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22	Total n=598 Participants Total of all reporting groups
Age, Continuous	59.1 years STANDARD_DEVIATION 9.6 • n=5 Participants	58.5 years STANDARD_DEVIATION 9.4 • n=7 Participants	58.8 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	124 Participants n=5 Participants	119 Participants n=7 Participants	243 Participants n=5 Participants
Sex: Female, Male Male	177 Participants n=5 Participants	178 Participants n=7 Participants	355 Participants n=5 Participants
Race/Ethnicity, Customized African	15 participants n=5 Participants	12 participants n=7 Participants	27 participants n=5 Participants
Race/Ethnicity, Customized Caucasian	217 participants n=5 Participants	204 participants n=7 Participants	421 participants n=5 Participants
Race/Ethnicity, Customized East Asian	54 participants n=5 Participants	68 participants n=7 Participants	122 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Native American	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized West Asian	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants
Race/Ethnicity, Customized Missing (unknown)	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Argentina	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United States	58 participants n=5 Participants	76 participants n=7 Participants	134 participants n=5 Participants
Region of Enrollment United Kingdom	14 participants n=5 Participants	5 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment Portugal	7 participants n=5 Participants	11 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Spain	38 participants n=5 Participants	27 participants n=7 Participants	65 participants n=5 Participants
Region of Enrollment India	14 participants n=5 Participants	14 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Greece	13 participants n=5 Participants	3 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Canada	16 participants n=5 Participants	10 participants n=7 Participants	26 participants n=5 Participants
Region of Enrollment Netherlands	26 participants n=5 Participants	20 participants n=7 Participants	46 participants n=5 Participants
Region of Enrollment Turkey	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Belgium	21 participants n=5 Participants	23 participants n=7 Participants	44 participants n=5 Participants
Region of Enrollment Ireland	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment China	27 participants n=5 Participants	34 participants n=7 Participants	61 participants n=5 Participants
Region of Enrollment Taiwan	11 participants n=5 Participants	14 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Brazil	7 participants n=5 Participants	9 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Korea, Republic of	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Australia	7 participants n=5 Participants	10 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment France	13 participants n=5 Participants	9 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Germany	15 participants n=5 Participants	22 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment Mexico	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
ECOG performance status 0	148 participants n=5 Participants	145 participants n=7 Participants	293 participants n=5 Participants
ECOG performance status 1	152 participants n=5 Participants	149 participants n=7 Participants	301 participants n=5 Participants
ECOG performance status Missing	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Disease stage Stage IIIA	140 participants n=5 Participants	142 participants n=7 Participants	282 participants n=5 Participants
Disease stage Stage IIIB	161 participants n=5 Participants	152 participants n=7 Participants	313 participants n=5 Participants
Disease stage Missing	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Histology Adenocarcinoma	226 participants n=5 Participants	226 participants n=7 Participants	452 participants n=5 Participants
Histology Large cell carcinoma	16 participants n=5 Participants	21 participants n=7 Participants	37 participants n=5 Participants
Histology Other	59 participants n=5 Participants	48 participants n=7 Participants	107 participants n=5 Participants
Histology Missing	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Smoking status Never smoked	50 participants n=5 Participants	58 participants n=7 Participants	108 participants n=5 Participants
Smoking status Moderate smoker	42 participants n=5 Participants	38 participants n=7 Participants	80 participants n=5 Participants
Smoking status Heavy smoker	190 participants n=5 Participants	183 participants n=7 Participants	373 participants n=5 Participants
Smoking status Missing	19 participants n=5 Participants	18 participants n=7 Participants	37 participants n=5 Participants
Baseline PET scan Yes	250 participants n=5 Participants	241 participants n=7 Participants	491 participants n=5 Participants
Baseline PET scan No	51 participants n=5 Participants	56 participants n=7 Participants	107 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Date of Death from Any Cause (Up to 71.4 Months)

Population: All randomized participants. Arm A had 124 participants censored and Arm B had 117 participants censored.

Outcome measures

Outcome measures
Measure	Arm A: Pemetrexed + Cisplatin and TRT n=301 Participants Participants were treated with Pemetrexed plus Cisplatin and concurrent TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gy per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles	Arm B: Etoposide + Cisplatin and TRT n=297 Participants Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m\^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m\^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m\^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22
Overall Survival	26.81 months Interval 20.4 to 30.92	24.97 months Interval 22.18 to 29.83

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease or Death from Any Cause (Up to 66.6 Months)

Population: All randomized participants. Arm A had 99 participants censored and Arm B had 87 participants censored.

Progression-free survival (PFS) time is from baseline to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have died or to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression or death, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy. PFS time was summarized using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Arm A: Pemetrexed + Cisplatin and TRT n=301 Participants Participants were treated with Pemetrexed plus Cisplatin and concurrent TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gy per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles	Arm B: Etoposide + Cisplatin and TRT n=297 Participants Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m\^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m\^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m\^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22
Progression-free Survival (PFS)	11.37 months Interval 10.25 to 13.21	9.76 months Interval 8.38 to 11.73

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease (Up to 7 Months)

Population: All randomized participants.

Overall response rate (ORR) is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.

Outcome measures

Outcome measures
Measure	Arm A: Pemetrexed + Cisplatin and TRT n=301 Participants Participants were treated with Pemetrexed plus Cisplatin and concurrent TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gy per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles	Arm B: Etoposide + Cisplatin and TRT n=297 Participants Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m\^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m\^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m\^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22
Objective Response Rate (Complete Response [CR] + Partial Response [PR])	35.9 percentage of participants Interval 30.46 to 41.58	33.0 percentage of participants Interval 27.67 to 38.66

SECONDARY outcome

Timeframe: Baseline to Date of Death from Any Cause (Up to 71.4 Months)

Population: All randomized participants. Arm A had 124 participants censored and Arm B had 117 participants censored.

The probability that survival time is at least 1, 2, or 3 years was summarized using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Arm A: Pemetrexed + Cisplatin and TRT n=301 Participants Participants were treated with Pemetrexed plus Cisplatin and concurrent TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gy per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles	Arm B: Etoposide + Cisplatin and TRT n=297 Participants Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m\^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m\^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m\^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22
Survival Rates at 1, 2, and 3 Years 1 year (12 months)	0.76 probability of survival Interval 0.7 to 0.8	0.77 probability of survival Interval 0.72 to 0.81
Survival Rates at 1, 2, and 3 Years 2 years (24 months)	0.52 probability of survival Interval 0.46 to 0.58	0.52 probability of survival Interval 0.46 to 0.58
Survival Rates at 1, 2, and 3 Years 3 years (36 months)	0.40 probability of survival Interval 0.34 to 0.46	0.37 probability of survival Interval 0.31 to 0.43

SECONDARY outcome

Timeframe: Baseline to Relapse (Up to 66.6 Months)

Population: All randomized participants with objective PD.

The percentage of participants with first sites of disease failure in terms of relapse within the radiation treatment field, inside the thorax, (outside of the radiation field), or distant disease are presented. Results were summarized using Kaplan-Meier estimates. Some participants relapsed in more than 1 location/site and appear in more than a single category.

Outcome measures

Outcome measures
Measure	Arm A: Pemetrexed + Cisplatin and TRT n=166 Participants Participants were treated with Pemetrexed plus Cisplatin and concurrent TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gy per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles	Arm B: Etoposide + Cisplatin and TRT n=190 Participants Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m\^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m\^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m\^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22
First Site of Disease Failure in Terms of Relapse Relapsed within the radiation treatment field	37.3 percentage of participants Interval 30.0 to 45.2	45.8 percentage of participants Interval 38.6 to 53.2
First Site of Disease Failure in Terms of Relapse Relapsed inside thorax, outside of radiation field	20.5 percentage of participants Interval 14.6 to 27.4	16.3 percentage of participants Interval 11.4 to 22.4
First Site of Disease Failure in Terms of Relapse Relapsed distant disease	50.0 percentage of participants Interval 42.2 to 57.8	45.8 percentage of participants Interval 38.6 to 53.2

SECONDARY outcome

Timeframe: Baseline through 30 Days Post Study

Population: All randomized participants with at least one post baseline swallowing diary score.

Participants were provided with a swallowing diary to record issues with swallowing using a 5-point categorical scale: (1) no problems; (2) mild soreness; (3) swallowing solids with some difficulty; (4) inability to swallow solids; and (5) inability to swallow liquids. Participants rated swallowing over the previous 24 hours. The percentage of participants was calculated by dividing the number of with a post baseline swallowing diary score \>=4 by total number of participants analyzed, multiplied by 100. No adjustments were made for the number of available assessments nor were any interpolation of missing assessments made.

Outcome measures

Outcome measures
Measure	Arm A: Pemetrexed + Cisplatin and TRT n=284 Participants Participants were treated with Pemetrexed plus Cisplatin and concurrent TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gy per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles	Arm B: Etoposide + Cisplatin and TRT n=269 Participants Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m\^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m\^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m\^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22
Percentage of Participants With a Post Baseline Swallowing Diary Score >=4	33.8 percentage of participants Interval 26.7 to 37.5	29.0 percentage of participants Interval 21.3 to 31.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline through 30 Days Post Study

Population: All randomized participants who received at least one dose of study drug.

The number of deaths that occurred while on study drug, the number of deaths due to adverse events (AEs) while on study drug, and the number of deaths due to the study disease (that is, disease progression) while on study drug are presented. In addition, the number of deaths within 30 days of treatment discontinuation, the number of deaths due to AEs within 30 days of treatment discontinuation, and the number of deaths due to study disease within 30 days of treatment discontinuation are presented. For both the deaths due to AEs that occurred on study and for deaths due to AEs that occurred within 30 days of treatment discontinuation, the causality (events assess as possibly related \[poss related\] to study drug per investigator judgement) is also presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	Arm A: Pemetrexed + Cisplatin and TRT n=283 Participants Participants were treated with Pemetrexed plus Cisplatin and concurrent TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gy per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles	Arm B: Etoposide + Cisplatin and TRT n=272 Participants Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m\^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m\^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m\^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22
Adverse Events: The Number of Deaths Per Treatment Group On study drug (total)	12 participants	6 participants
Adverse Events: The Number of Deaths Per Treatment Group On study drug: Due to AE	10 participants	4 participants
Adverse Events: The Number of Deaths Per Treatment Group On study drug: Due to AE poss related	5 participants	3 participants
Adverse Events: The Number of Deaths Per Treatment Group On study drug: Due to study disease	2 participants	0 participants
Adverse Events: The Number of Deaths Per Treatment Group Within 30 Days of Discontinuation (disc) (total)	10 participants	6 participants
Adverse Events: The Number of Deaths Per Treatment Group Within 30 Days of Disc: Due to AE	5 participants	4 participants
Adverse Events: The Number of Deaths Per Treatment Group Within 30 Days of Disc: Due to AE poss related	2 participants	0 participants
Adverse Events: The Number of Deaths Per Treatment Group Within 30 Days of Disc: Due to study disease	5 participants	2 participants

Adverse Events

Arm A:

Serious events: 134 serious events

Other events: 279 other events

Deaths: 0 deaths

Arm B: Etoposide + Cisplatin and TRT

Serious events: 145 serious events

Other events: 269 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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

Measure	Arm A: n=283 participants at risk Arm A: Participants were treated with pemetrexed plus cisplatin and concurrent thoracic radiation TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for four 21-day cycles Concurrent Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on day 1 of chemotherapy, once daily fractions (2 Gy per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles.	Arm B: Etoposide + Cisplatin and TRT n=272 participants at risk Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase
Blood and lymphatic system disorders Anaemia	31.1% 88/283 • Number of events 336 Randomized participants who received at least one dose of study drug.	34.6% 94/272 • Number of events 312 Randomized participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	22.3% 63/283 • Number of events 267 Randomized participants who received at least one dose of study drug.	26.1% 71/272 • Number of events 237 Randomized participants who received at least one dose of study drug.
Blood and lymphatic system disorders Lymphopenia	21.9% 62/283 • Number of events 297 Randomized participants who received at least one dose of study drug.	17.3% 47/272 • Number of events 170 Randomized participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	32.5% 92/283 • Number of events 252 Randomized participants who received at least one dose of study drug.	45.2% 123/272 • Number of events 359 Randomized participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	13.8% 39/283 • Number of events 116 Randomized participants who received at least one dose of study drug.	19.5% 53/272 • Number of events 132 Randomized participants who received at least one dose of study drug.
Ear and labyrinth disorders Tinnitus	5.3% 15/283 • Number of events 40 Randomized participants who received at least one dose of study drug.	2.9% 8/272 • Number of events 27 Randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	12.4% 35/283 • Number of events 94 Randomized participants who received at least one dose of study drug.	2.9% 8/272 • Number of events 13 Randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	39.6% 112/283 • Number of events 312 Randomized participants who received at least one dose of study drug.	47.4% 129/272 • Number of events 284 Randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	19.4% 55/283 • Number of events 88 Randomized participants who received at least one dose of study drug.	23.2% 63/272 • Number of events 104 Randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	15.2% 43/283 • Number of events 148 Randomized participants who received at least one dose of study drug.	13.6% 37/272 • Number of events 95 Randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Dysphagia	49.5% 140/283 • Number of events 567 Randomized participants who received at least one dose of study drug.	40.4% 110/272 • Number of events 317 Randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	61.8% 175/283 • Number of events 532 Randomized participants who received at least one dose of study drug.	52.9% 144/272 • Number of events 365 Randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Odynophagia	8.5% 24/283 • Number of events 103 Randomized participants who received at least one dose of study drug.	8.5% 23/272 • Number of events 56 Randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Oesophagitis	42.0% 119/283 • Number of events 470 Randomized participants who received at least one dose of study drug.	36.4% 99/272 • Number of events 253 Randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Stomatitis	9.2% 26/283 • Number of events 50 Randomized participants who received at least one dose of study drug.	4.4% 12/272 • Number of events 23 Randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	38.9% 110/283 • Number of events 244 Randomized participants who received at least one dose of study drug.	34.9% 95/272 • Number of events 173 Randomized participants who received at least one dose of study drug.
General disorders Asthenia	22.6% 64/283 • Number of events 249 Randomized participants who received at least one dose of study drug.	12.9% 35/272 • Number of events 101 Randomized participants who received at least one dose of study drug.
General disorders Chest pain	14.1% 40/283 • Number of events 154 Randomized participants who received at least one dose of study drug.	11.8% 32/272 • Number of events 71 Randomized participants who received at least one dose of study drug.
General disorders Fatigue	49.1% 139/283 • Number of events 685 Randomized participants who received at least one dose of study drug.	48.2% 131/272 • Number of events 472 Randomized participants who received at least one dose of study drug.
General disorders Mucosal inflammation	11.0% 31/283 • Number of events 73 Randomized participants who received at least one dose of study drug.	8.5% 23/272 • Number of events 64 Randomized participants who received at least one dose of study drug.
General disorders Oedema peripheral	8.5% 24/283 • Number of events 61 Randomized participants who received at least one dose of study drug.	4.4% 12/272 • Number of events 28 Randomized participants who received at least one dose of study drug.
General disorders Pyrexia	19.8% 56/283 • Number of events 76 Randomized participants who received at least one dose of study drug.	15.4% 42/272 • Number of events 60 Randomized participants who received at least one dose of study drug.
Infections and infestations Pneumonia	6.0% 17/283 • Number of events 36 Randomized participants who received at least one dose of study drug.	4.4% 12/272 • Number of events 21 Randomized participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	5.3% 15/283 • Number of events 29 Randomized participants who received at least one dose of study drug.	4.0% 11/272 • Number of events 18 Randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Radiation oesophagitis	5.7% 16/283 • Number of events 50 Randomized participants who received at least one dose of study drug.	6.6% 18/272 • Number of events 42 Randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Radiation pneumonitis	7.8% 22/283 • Number of events 52 Randomized participants who received at least one dose of study drug.	5.9% 16/272 • Number of events 29 Randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Radiation skin injury	15.9% 45/283 • Number of events 159 Randomized participants who received at least one dose of study drug.	13.6% 37/272 • Number of events 81 Randomized participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	7.4% 21/283 • Number of events 84 Randomized participants who received at least one dose of study drug.	4.0% 11/272 • Number of events 25 Randomized participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	7.1% 20/283 • Number of events 63 Randomized participants who received at least one dose of study drug.	3.3% 9/272 • Number of events 18 Randomized participants who received at least one dose of study drug.
Investigations Blood creatinine increased	9.2% 26/283 • Number of events 67 Randomized participants who received at least one dose of study drug.	5.9% 16/272 • Number of events 32 Randomized participants who received at least one dose of study drug.
Investigations Haemoglobin decreased	17.0% 48/283 • Number of events 218 Randomized participants who received at least one dose of study drug.	15.8% 43/272 • Number of events 155 Randomized participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	11.3% 32/283 • Number of events 115 Randomized participants who received at least one dose of study drug.	11.4% 31/272 • Number of events 76 Randomized participants who received at least one dose of study drug.
Investigations Platelet count decreased	8.5% 24/283 • Number of events 74 Randomized participants who received at least one dose of study drug.	12.1% 33/272 • Number of events 78 Randomized participants who received at least one dose of study drug.
Investigations Weight decreased	24.4% 69/283 • Number of events 257 Randomized participants who received at least one dose of study drug.	22.4% 61/272 • Number of events 204 Randomized participants who received at least one dose of study drug.
Investigations White blood cell count decreased	16.6% 47/283 • Number of events 212 Randomized participants who received at least one dose of study drug.	15.8% 43/272 • Number of events 131 Randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	36.7% 104/283 • Number of events 366 Randomized participants who received at least one dose of study drug.	32.4% 88/272 • Number of events 228 Randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	6.7% 19/283 • Number of events 31 Randomized participants who received at least one dose of study drug.	8.8% 24/272 • Number of events 38 Randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	5.7% 16/283 • Number of events 57 Randomized participants who received at least one dose of study drug.	2.9% 8/272 • Number of events 25 Randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	7.1% 20/283 • Number of events 43 Randomized participants who received at least one dose of study drug.	11.8% 32/272 • Number of events 49 Randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypomagnesaemia	7.8% 22/283 • Number of events 84 Randomized participants who received at least one dose of study drug.	11.8% 32/272 • Number of events 84 Randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	6.7% 19/283 • Number of events 52 Randomized participants who received at least one dose of study drug.	8.1% 22/272 • Number of events 55 Randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	4.6% 13/283 • Number of events 33 Randomized participants who received at least one dose of study drug.	6.2% 17/272 • Number of events 30 Randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	9.2% 26/283 • Number of events 94 Randomized participants who received at least one dose of study drug.	7.7% 21/272 • Number of events 51 Randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	5.3% 15/283 • Number of events 41 Randomized participants who received at least one dose of study drug.	4.0% 11/272 • Number of events 17 Randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	3.9% 11/283 • Number of events 26 Randomized participants who received at least one dose of study drug.	5.1% 14/272 • Number of events 30 Randomized participants who received at least one dose of study drug.
Nervous system disorders Dizziness	17.7% 50/283 • Number of events 152 Randomized participants who received at least one dose of study drug.	16.5% 45/272 • Number of events 96 Randomized participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	11.0% 31/283 • Number of events 122 Randomized participants who received at least one dose of study drug.	8.1% 22/272 • Number of events 60 Randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	12.7% 36/283 • Number of events 92 Randomized participants who received at least one dose of study drug.	12.5% 34/272 • Number of events 67 Randomized participants who received at least one dose of study drug.
Nervous system disorders Neuropathy peripheral	4.9% 14/283 • Number of events 35 Randomized participants who received at least one dose of study drug.	9.2% 25/272 • Number of events 64 Randomized participants who received at least one dose of study drug.
Nervous system disorders Peripheral sensory neuropathy	8.1% 23/283 • Number of events 80 Randomized participants who received at least one dose of study drug.	7.7% 21/272 • Number of events 61 Randomized participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	6.0% 17/283 • Number of events 61 Randomized participants who received at least one dose of study drug.	4.4% 12/272 • Number of events 35 Randomized participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	18.4% 52/283 • Number of events 175 Randomized participants who received at least one dose of study drug.	15.4% 42/272 • Number of events 126 Randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	37.1% 105/283 • Number of events 430 Randomized participants who received at least one dose of study drug.	30.9% 84/272 • Number of events 273 Randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	32.9% 93/283 • Number of events 308 Randomized participants who received at least one dose of study drug.	19.5% 53/272 • Number of events 142 Randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Hiccups	11.0% 31/283 • Number of events 84 Randomized participants who received at least one dose of study drug.	6.2% 17/272 • Number of events 33 Randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.0% 17/283 • Number of events 43 Randomized participants who received at least one dose of study drug.	8.8% 24/272 • Number of events 41 Randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumonitis	8.1% 23/283 • Number of events 59 Randomized participants who received at least one dose of study drug.	2.9% 8/272 • Number of events 23 Randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	8.5% 24/283 • Number of events 110 Randomized participants who received at least one dose of study drug.	37.9% 103/272 • Number of events 389 Randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	4.2% 12/283 • Number of events 52 Randomized participants who received at least one dose of study drug.	5.5% 15/272 • Number of events 43 Randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Erythema	6.0% 17/283 • Number of events 50 Randomized participants who received at least one dose of study drug.	4.8% 13/272 • Number of events 29 Randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	6.4% 18/283 • Number of events 55 Randomized participants who received at least one dose of study drug.	4.0% 11/272 • Number of events 19 Randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	15.9% 45/283 • Number of events 110 Randomized participants who received at least one dose of study drug.	14.7% 40/272 • Number of events 93 Randomized participants who received at least one dose of study drug.
Vascular disorders Hypotension	1.1% 3/283 • Number of events 6 Randomized participants who received at least one dose of study drug.	5.9% 16/272 • Number of events 40 Randomized participants who received at least one dose of study drug.