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A Study of Atezolizumab in Combination With Carboplatin + Paclitaxel or Carboplatin + Nab-Paclitaxel Compared With Carboplatin + Nab-Paclitaxel in Participants With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC) [IMpower131]

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ClinicalTrials.gov Identifier: NCT02367794
Recruitment Status : Completed
First Posted : February 20, 2015
Results First Posted : November 12, 2019
Last Update Posted : April 13, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Squamous Non-Small Cell Lung Cancer
Interventions Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (anti-PD-L1) antibody
Drug: Carboplatin
Drug: Nab-Paclitaxel
Drug: Paclitaxel
Enrollment 1021
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description The induction phase of the study consisted of four or six cycles; carboplatin was administered on Day 1 of each 21-day cycle, nab-paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: nab-paclitaxel, then carboplatin. Participants who experienced disease progression at any time during the induction phase discontinued all study treatment. In the maintenance phase, participants received best supportive care. The induction phase of the study consisted of four or six cycles; atezolizumab and carboplatin were administered on Day 1 of each 21-day cycle. Nab-Paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then nab-paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant. The induction phase of the study consisted of four or six cycles; atezolizumab, paclitaxel, and carboplatin were administered on Day 1 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant.
Period Title: Overall Study
Started 340 343 338
Completed 82 103 89
Not Completed 258 240 249
Reason Not Completed
Death             230             223             229
Lost to Follow-up             1             2             1
Physician Decision             0             3             1
Protocol Violation             1             0             1
Withdrawal by Subject             25             12             14
Brain metastasis             1             0             0
Randomized in error             0             0             1
Patient unable to receive carboplatin             0             0             1
Hypercalcemia prior to C1D1             0             0             1
Arm/Group Title Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin Total
Hide Arm/Group Description The induction phase of the study consisted of four or six cycles; carboplatin was administered on Day 1 of each 21-day cycle, nab-paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: nab-paclitaxel, then carboplatin. Participants who experienced disease progression at any time during the induction phase discontinued all study treatment. In the maintenance phase, participants received best supportive care. The induction phase of the study consisted of four or six cycles; atezolizumab and carboplatin were administered on Day 1 of each 21-day cycle. Nab-Paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then nab-paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant. The induction phase of the study consisted of four or six cycles; atezolizumab, paclitaxel, and carboplatin were administered on Day 1 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant. Total of all reporting groups
Overall Number of Baseline Participants 340 343 338 1021
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 340 participants 343 participants 338 participants 1021 participants
64.9  (8.1) 64.0  (9.2) 65.0  (8.3) 64.6  (8.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 340 participants 343 participants 338 participants 1021 participants
Female
63
  18.5%
63
  18.4%
60
  17.8%
186
  18.2%
Male
277
  81.5%
280
  81.6%
278
  82.2%
835
  81.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 340 participants 343 participants 338 participants 1021 participants
Hispanic or Latino
24
   7.1%
27
   7.9%
28
   8.3%
79
   7.7%
Not Hispanic or Latino
299
  87.9%
306
  89.2%
297
  87.9%
902
  88.3%
Unknown or Not Reported
17
   5.0%
10
   2.9%
13
   3.8%
40
   3.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 340 participants 343 participants 338 participants 1021 participants
American Indian or Alaska Native
1
   0.3%
1
   0.3%
3
   0.9%
5
   0.5%
Asian
37
  10.9%
41
  12.0%
34
  10.1%
112
  11.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   0.3%
1
   0.1%
Black or African American
7
   2.1%
4
   1.2%
3
   0.9%
14
   1.4%
White
290
  85.3%
289
  84.3%
290
  85.8%
869
  85.1%
More than one race
1
   0.3%
6
   1.7%
1
   0.3%
8
   0.8%
Unknown or Not Reported
4
   1.2%
2
   0.6%
6
   1.8%
12
   1.2%
1.Primary Outcome
Title Progression Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population
Hide Description PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the ITT population.
Time Frame Up to approximately 30 months after first participant enrolled
Hide Outcome Measure Data
Hide Analysis Population Description
Intent To Treat (ITT) was defined as all randomized participants, irrespective of whether the assigned treatment was actually received.
Arm/Group Title Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
The induction phase of the study consisted of four or six cycles; carboplatin was administered on Day 1 of each 21-day cycle, nab-paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: nab-paclitaxel, then carboplatin. Participants who experienced disease progression at any time during the induction phase discontinued all study treatment. In the maintenance phase, participants received best supportive care.
The induction phase of the study consisted of four or six cycles; atezolizumab and carboplatin were administered on Day 1 of each 21-day cycle. Nab-Paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then nab-paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant.
The induction phase of the study consisted of four or six cycles; atezolizumab, paclitaxel, and carboplatin were administered on Day 1 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant.
Overall Number of Participants Analyzed 340 343 338
Median (95% Confidence Interval)
Unit of Measure: Months
5.6
(5.5 to 5.7)
6.5
(5.7 to 7.1)
5.6
(5.5 to 6.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm C: Nab-Paclitaxel + Carboplatin, Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.64 to 0.88
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival (OS) in the ITT Population
Hide Description OS is defined as the time between the date of randomization and date of death from any cause in the ITT population.
Time Frame Up to approximately 39 months after first participant enrolled
Hide Outcome Measure Data
Hide Analysis Population Description
Intent To Treat (ITT) was defined as all randomized participants, irrespective of whether the assigned treatment was actually received.
Arm/Group Title Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
The induction phase of the study consisted of four or six cycles; carboplatin was administered on Day 1 of each 21-day cycle, nab-paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: nab-paclitaxel, then carboplatin. Participants who experienced disease progression at any time during the induction phase discontinued all study treatment. In the maintenance phase, participants received best supportive care.
The induction phase of the study consisted of four or six cycles; atezolizumab and carboplatin were administered on Day 1 of each 21-day cycle. Nab-Paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then nab-paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant.
The induction phase of the study consisted of four or six cycles; atezolizumab, paclitaxel, and carboplatin were administered on Day 1 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant.
Overall Number of Participants Analyzed 340 343 338
Median (95% Confidence Interval)
Unit of Measure: Months
13.5
(12.2 to 15.1)
14.2
(12.3 to 16.8)
12.6
(11.6 to 14.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm C: Nab-Paclitaxel + Carboplatin, Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1581
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.73 to 1.05
Estimation Comments [Not Specified]
3.Secondary Outcome
Title OS in the Tumor Gene Expression (tGE) Population
Hide Description [Not Specified]
Time Frame Up to approximately 39 months after first participant enrolled
Outcome Measure Data Not Reported
4.Secondary Outcome
Title PFS as Determined by the Investigator Using RECIST v1.1 in the tGE Population
Hide Description [Not Specified]
Time Frame Up to approximately 30 months after first participant enrolled
Outcome Measure Data Not Reported
5.Secondary Outcome
Title PFS as Determined by the Investigator Using RECIST v1.1 in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population
Hide Description [Not Specified]
Time Frame Up to approximately 30 months after first participant enrolled
Outcome Measure Data Not Reported
6.Secondary Outcome
Title PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population
Hide Description [Not Specified]
Time Frame Up to approximately 30 months after first participant enrolled
Outcome Measure Data Not Reported
7.Secondary Outcome
Title OS in the TC2/3 or IC2/3 Population
Hide Description [Not Specified]
Time Frame Up to approximately 39 months after first participant enrolled
Outcome Measure Data Not Reported
8.Secondary Outcome
Title OS in the TC1/2/3 or IC1/2/3 Population
Hide Description [Not Specified]
Time Frame Up to approximately 39 months after first participant enrolled
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population
Hide Description [Not Specified]
Time Frame Up to approximately 30 months after first participant enrolled
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population
Hide Description [Not Specified]
Time Frame Up to approximately 30 months after first participant enrolled
Outcome Measure Data Not Reported
11.Secondary Outcome
Title OS at 1 and 2 Years in the ITT Population
Hide Description OS rates at 1 and 2 years is defined as the proportion of participants alive at 1 and 2 years after randomization estimated using Kaplan-Meier (KM) methodology for the ITT population
Time Frame 1 and 2 years
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population
Hide Description [Not Specified]
Time Frame Up to approximately 30 months after first participant enrolled
Outcome Measure Data Not Reported
13.Secondary Outcome
Title TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-LC13 Symptom Subscales in the ITT Population
Hide Description [Not Specified]
Time Frame Up to approximately 30 months after the first participant enrolled
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Change From Baseline in Patient-reported Lung Cancer Symptoms Score Using the SILC Scale Symptom Severity Score in the ITT Population
Hide Description [Not Specified]
Time Frame Baseline up to approximately 30 months after first participant enrolled
Outcome Measure Data Not Reported
15.Secondary Outcome
Title PFS as Determined by the Investigator Using RECIST v1.1 in the ITT Population (Arm A vs. Arm B)
Hide Description [Not Specified]
Time Frame Up to approximately 30 months after first participant enrolled
Outcome Measure Data Not Reported
16.Secondary Outcome
Title OS in the ITT Population (Arm A vs. Arm B)
Hide Description [Not Specified]
Time Frame Up to approximately 39 months after first participant enrolled
Outcome Measure Data Not Reported
17.Secondary Outcome
Title Percentage of Participants With Adverse Events
Hide Description [Not Specified]
Time Frame Up to approximately 39 months after first participant enrolled
Outcome Measure Data Not Reported
18.Secondary Outcome
Title Percentage of Participants With Anti-therapeutic Antibody (ATA) Response to Atezolizumab
Hide Description The predose samples will be collected on the same day of treatment administration.
Time Frame Predose on Day 1 of Cycles 1-4, 8, 16, every 8 cycle thereafter (up to 39 months), at treatment discontinuation (up to 39 months), and at 120 days after the last dose of atezolizumab (up to approximately 39 months, each cycle is 21 days)
Outcome Measure Data Not Reported
19.Secondary Outcome
Title Maximum Observed Serum Atezolizumab Concentration (Cmax)
Hide Description The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes.
Time Frame Predose on Day 1 of Cycles 1-4, 8, 16, every 8 cycle up to 39 months; 30 minutes postdose on Day 1 of Cycles 1 and 3; at treatment discontinuation (up to 39 months), and at 120 days after last dose of atezolizumab (up to 39 months, each cycle is 21 days)
Outcome Measure Data Not Reported
20.Secondary Outcome
Title Minimum Observed Serum Atezolizumab Concentration (Cmin)
Hide Description The predose samples will be collected on the same day of treatment administration.
Time Frame Predose on Day 1 of Cycles 1-4, 8, 16, every 8 cycle thereafter (up to 39 months), at treatment discontinuation (up to 39 months), and at 120 days after the last dose of atezolizumab (up to approximately 39 months, each cycle is 21 days)
Outcome Measure Data Not Reported
21.Secondary Outcome
Title Plasma Concentrations for Paclitaxel
Hide Description [Not Specified]
Time Frame Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 180 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)
Outcome Measure Data Not Reported
22.Secondary Outcome
Title Plasma Concentrations for Nab-Paclitaxel
Hide Description [Not Specified]
Time Frame Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)
Outcome Measure Data Not Reported
23.Secondary Outcome
Title Plasma Concentrations for Carboplatin
Hide Description [Not Specified]
Time Frame Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 15 to 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)
Outcome Measure Data Not Reported
Time Frame From the first study drug administration to the data cutoff date: 3 October 2018 (up to approximately 40 months).
Adverse Event Reporting Description Safety-evaluable population included all participants who received at least one dose of any study medication.
 
Arm/Group Title Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description The induction phase of the study consisted of four or six cycles; carboplatin was administered on Day 1 of each 21-day cycle, nab-paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: nab-paclitaxel, then carboplatin. Participants who experienced disease progression at any time during the induction phase discontinued all study treatment. In the maintenance phase, participants received best supportive care. The induction phase of the study consisted of four or six cycles; atezolizumab and carboplatin were administered on Day 1 of each 21-day cycle. Nab-Paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then nab-paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant. The induction phase of the study consisted of four or six cycles; atezolizumab, paclitaxel, and carboplatin were administered on Day 1 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant.
All-Cause Mortality
Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   230/340 (67.65%)      223/343 (65.01%)      229/338 (67.75%)    
Hide Serious Adverse Events
Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   96/334 (28.74%)      143/334 (42.81%)      160/332 (48.19%)    
Blood and lymphatic system disorders       
Anaemia  1  3/334 (0.90%)  3 7/334 (2.10%)  7 6/332 (1.81%)  6
Ferbrile Neutropenia  1  5/334 (1.50%)  5 13/334 (3.89%)  15 16/332 (4.82%)  16
Haemolysis  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Neutropenia  1  3/334 (0.90%)  3 3/334 (0.90%)  3 2/332 (0.60%)  2
Pancytopenia  1  2/334 (0.60%)  2 0/334 (0.00%)  0 0/332 (0.00%)  0
Thrombocytopenia  1  1/334 (0.30%)  1 2/334 (0.60%)  2 1/332 (0.30%)  1
Cardiac disorders       
Acute Myocardial Infarction  1  1/334 (0.30%)  1 2/334 (0.60%)  2 2/332 (0.60%)  2
Arrhythmia  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Atrial Fibrillation  1  3/334 (0.90%)  3 2/334 (0.60%)  3 6/332 (1.81%)  6
Atrial Flutter  1  1/334 (0.30%)  1 0/334 (0.00%)  0 5/332 (1.51%)  5
Atrial Thrombosis  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Bradycardia  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Cardiac Arrest  1  0/334 (0.00%)  0 0/334 (0.00%)  0 2/332 (0.60%)  2
Cardiac Failure  1  1/334 (0.30%)  2 2/334 (0.60%)  2 1/332 (0.30%)  1
Cardiac Failure Acute  1  2/334 (0.60%)  2 0/334 (0.00%)  0 2/332 (0.60%)  2
Cardiac Tamponade  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Cardio-Respiratory Arrest  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Coronary Artery Stenosis  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Left Ventricular Dysfunction  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Myocardial Infarction  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Pericardial Effusion  1  0/334 (0.00%)  0 4/334 (1.20%)  4 0/332 (0.00%)  0
Sinus Tachycardia  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Tachycardia  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Congenital, familial and genetic disorders       
Tracheo-Oesophageal Fistula  1  0/334 (0.00%)  0 1/334 (0.30%)  1 1/332 (0.30%)  1
Endocrine disorders       
Adrenal Insufficiency  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Hyperthyroidism  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Hypopituitarism  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Eye disorders       
Retinal Detachment  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Gastrointestinal disorders       
Abdominal Pain  1  1/334 (0.30%)  1 1/334 (0.30%)  1 1/332 (0.30%)  1
Abdominal Pain Upper  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Anal Haemorrhage  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Colitis  1  0/334 (0.00%)  0 3/334 (0.90%)  3 1/332 (0.30%)  1
Constipation  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Diarrhoea  1  4/334 (1.20%)  5 6/334 (1.80%)  6 3/332 (0.90%)  4
Duodenal Perforation  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Dysphagia  1  0/334 (0.00%)  0 0/334 (0.00%)  0 2/332 (0.60%)  2
Enterocolitis  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Gastritis  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Gastrointestinal Haemorrhage  1  2/334 (0.60%)  2 1/334 (0.30%)  1 0/332 (0.00%)  0
Gastrointestinal Necrosis  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Gastrointestinal Perforation  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Gastrointestinal Toxicity  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Inguinal Hernia  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Intestinal Perforation  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Large Intestine Perforation  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Nausea  1  1/334 (0.30%)  1 1/334 (0.30%)  1 0/332 (0.00%)  0
Oesophagitis  1  0/334 (0.00%)  0 1/334 (0.30%)  1 1/332 (0.30%)  1
Pancreatitis  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Pancreatitis Chronic  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Rectal Haemorrhage  1  0/334 (0.00%)  0 1/334 (0.30%)  2 0/332 (0.00%)  0
Small Intestinal Obstruction  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Upper Gastrointestinal Haemorrhage  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Vomiting  1  1/334 (0.30%)  1 1/334 (0.30%)  1 2/332 (0.60%)  2
General disorders       
Asthenia  1  1/334 (0.30%)  2 0/334 (0.00%)  0 2/332 (0.60%)  2
Chest Pain  1  2/334 (0.60%)  2 0/334 (0.00%)  0 3/332 (0.90%)  4
Death  1  0/334 (0.00%)  0 7/334 (2.10%)  7 2/332 (0.60%)  2
Fatigue  1  0/334 (0.00%)  0 3/334 (0.90%)  3 1/332 (0.30%)  1
Gait Disturbance  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Malaise  1  1/334 (0.30%)  1 2/334 (0.60%)  2 0/332 (0.00%)  0
Mucosal Inflammation  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Non-Cardiac Chest Pain  1  1/334 (0.30%)  1 0/334 (0.00%)  0 1/332 (0.30%)  1
Oedema  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Pain  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Performance Status Decreased  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Pyrexia  1  5/334 (1.50%)  6 5/334 (1.50%)  5 5/332 (1.51%)  7
Hepatobiliary disorders       
Autoimmune Hepatitis  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Bile Duct Stone  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Cholecystitis  1  1/334 (0.30%)  1 1/334 (0.30%)  1 1/332 (0.30%)  2
Cholecystitis Acute  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Drug-Induced Liver Injury  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Hepatic Function Abnormal  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Hepatitis  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Hepatitis Toxic  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Immune-Medicated Hepatitis  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Immune system disorders       
Anaphylactic Reaction  1  0/334 (0.00%)  0 0/334 (0.00%)  0 2/332 (0.60%)  2
Drug Hypersensitivity  1  0/334 (0.00%)  0 0/334 (0.00%)  0 2/332 (0.60%)  2
Haemophagocytic Lymphohistiocytosis  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Infections and infestations       
Abdominal Infection  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Appendicitis  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Bacteraemia  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Bronchitis  1  1/334 (0.30%)  1 3/334 (0.90%)  3 5/332 (1.51%)  5
Cellulitis  1  1/334 (0.30%)  1 1/334 (0.30%)  1 0/332 (0.00%)  0
Clostridium Difficle Infection  1  0/334 (0.00%)  0 2/334 (0.60%)  2 0/332 (0.00%)  0
Colonic Abscess  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Device Related Infection  1  0/334 (0.00%)  0 1/334 (0.30%)  2 0/332 (0.00%)  0
Endocarditis  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Enterocolitis Infection  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Gastroenteritis  1  0/334 (0.00%)  0 2/334 (0.60%)  2 0/332 (0.00%)  0
Hepatitis B  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Infected Dermal Cyst  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Infection  1  0/334 (0.00%)  0 1/334 (0.30%)  1 1/332 (0.30%)  1
Infection Exacerbation of Chronic Obstructive Ariways Disease  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Influenza  1  0/334 (0.00%)  0 1/334 (0.30%)  1 1/332 (0.30%)  1
Lower Respiratory Tract Infection  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Lung Abscess  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Lung Infection  1  7/334 (2.10%)  7 1/334 (0.30%)  1 5/332 (1.51%)  5
Meningitis  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Pleural Infection  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Pneumonia  1  14/334 (4.19%)  14 30/334 (8.98%)  34 25/332 (7.53%)  27
Pneumonia Bacterial  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Pneumonia Haemophilus  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Pneumonia Staphylococcal  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Pneumonia Streptococcal  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Pseudomonal Sepsis  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Pulmonary Sepsis  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  2
Respiratory Tract Infection  1  3/334 (0.90%)  3 2/334 (0.60%)  3 2/332 (0.60%)  3
Sepsis  1  6/334 (1.80%)  6 5/334 (1.50%)  5 9/332 (2.71%)  10
Septic Shock  1  1/334 (0.30%)  1 3/334 (0.90%)  3 1/332 (0.30%)  1
Sinusitis  1  1/334 (0.30%)  1 1/334 (0.30%)  1 0/332 (0.00%)  0
Stomatococcal Infection  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Upper Respiratory Tract Infection  1  0/334 (0.00%)  0 2/334 (0.60%)  2 1/332 (0.30%)  1
Urinary Tract Infection  1  3/334 (0.90%)  3 2/334 (0.60%)  2 0/332 (0.00%)  0
Urinary Tract Infection Staphylococcal  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Urosepsis  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Injury, poisoning and procedural complications       
Alcohol Poisoning  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Chest Injury  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Fall  1  0/334 (0.00%)  0 1/334 (0.30%)  1 1/332 (0.30%)  1
Fermur Fracture  1  0/334 (0.00%)  0 1/334 (0.30%)  1 1/332 (0.30%)  1
Hip Fracture  1  0/334 (0.00%)  0 2/334 (0.60%)  2 2/332 (0.60%)  2
Humerus Fracture  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Infusion Related Reaction  1  0/334 (0.00%)  0 0/334 (0.00%)  0 2/332 (0.60%)  2
Periorbital Haematoma  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Radiation Oesophagitis  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Radiation Pneumonitis  1  0/334 (0.00%)  0 2/334 (0.60%)  2 1/332 (0.30%)  1
Rib Facture  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Skin Laceration  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Subdural Haematoma  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Thoracic Vertebral Fracture  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Toxicity to Various Agents  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Investigations       
Blood Bilirubin Increased  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Blood Creatinine Increased  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Blood Lactic Acid Increased  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
General Physical Condition Abnormal  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  2
Liver Function Test Abnormal  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Neutrophil Count Decreased  1  1/334 (0.30%)  1 1/334 (0.30%)  1 3/332 (0.90%)  3
Platelet Count Decreased  1  2/334 (0.60%)  2 1/334 (0.30%)  1 0/332 (0.00%)  0
Weight Decreased  1  0/334 (0.00%)  0 1/334 (0.30%)  1 1/332 (0.30%)  1
Metabolism and nutrition disorders       
Decreased Appetite  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Dehydration  1  2/334 (0.60%)  2 3/334 (0.90%)  3 4/332 (1.20%)  4
Diabetes Mellitus  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Failure to Thrive  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Hypercalcaemia  1  2/334 (0.60%)  2 1/334 (0.30%)  1 2/332 (0.60%)  2
Hyperglycaemia  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Hyperkalaemia  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Hypocalcaemia  1  0/334 (0.00%)  0 2/334 (0.60%)  2 0/332 (0.00%)  0
Hypomagnesaemia  1  0/334 (0.00%)  0 2/334 (0.60%)  2 0/332 (0.00%)  0
Hyponatraemia  1  3/334 (0.90%)  3 2/334 (0.60%)  2 1/332 (0.30%)  1
Type 2 Diabetes Mellitus  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Back Pain  1  0/334 (0.00%)  0 0/334 (0.00%)  0 5/332 (1.51%)  5
Flank Pain  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Musculoskeletal Chest Pain  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Musculoskeletal Pain  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Pathological Fracture  1  0/334 (0.00%)  0 1/334 (0.30%)  1 1/332 (0.30%)  1
Polyarthritis  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Polymyositis  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Benign Salivary Gland Neoplasm  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Colon Cancer  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Gallbladder Adenocarcinoma  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Infected Neoplasm  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Prostate Cancer  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Tumour Embolism  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Nervous system disorders       
Brain Oedema  1  1/334 (0.30%)  1 0/334 (0.00%)  0 1/332 (0.30%)  1
Cerebral Ischaemia  1  1/334 (0.30%)  1 1/334 (0.30%)  1 0/332 (0.00%)  0
Cerebrovascular Accident  1  1/334 (0.30%)  1 0/334 (0.00%)  0 4/332 (1.20%)  4
Depressed Level of Consciousness  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Dizziness  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Embolic Stroke  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Epilepsy  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Guillain-Barre Syndrome  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Hemiplegia  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Hyperaesthesia  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Hypotonia  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Ischaemic Stroke  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Motor Dysfunction  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Myxoedema Coma  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Paraesthesia  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Seizure  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Spinal Cord Compression  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Syncope  1  0/334 (0.00%)  0 2/334 (0.60%)  2 0/332 (0.00%)  0
Product Issues       
Device Dislocation  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Psychiatric disorders       
Completed Suicide  1  0/334 (0.00%)  0 2/334 (0.60%)  2 0/332 (0.00%)  0
Confusional State  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Depression  1  1/334 (0.30%)  1 0/334 (0.00%)  0 1/332 (0.30%)  1
Hallucination  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Mental Status Changes  1  0/334 (0.00%)  0 2/334 (0.60%)  2 0/332 (0.00%)  0
Suicide Ideation  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Renal and urinary disorders       
Acute Kidney Injury  1  1/334 (0.30%)  1 4/334 (1.20%)  4 2/332 (0.60%)  2
Hydronephrosis  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Urinary Retention  1  1/334 (0.30%)  1 2/334 (0.60%)  3 1/332 (0.30%)  1
Reproductive system and breast disorders       
Prostatitis  1  0/334 (0.00%)  0 2/334 (0.60%)  2 0/332 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Aspiration  1  0/334 (0.00%)  0 1/334 (0.30%)  1 1/332 (0.30%)  1
Atelectasis  1  1/334 (0.30%)  1 0/334 (0.00%)  0 0/332 (0.00%)  0
Bronchial Haemorrhage  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Chronic Obstructive Pulmonary Disease  1  3/334 (0.90%)  3 6/334 (1.80%)  6 10/332 (3.01%)  14
Cough  1  0/334 (0.00%)  0 0/334 (0.00%)  0 2/332 (0.60%)  2
Diaphragmatic Paralysis  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Dyspnoea  1  3/334 (0.90%)  4 6/334 (1.80%)  7 6/332 (1.81%)  6
Dyspnoea at Rest  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Dyspnoea Exertional  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Emphysema  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Epistaxis  1  1/334 (0.30%)  1 1/334 (0.30%)  1 0/332 (0.00%)  0
Haemoptysis  1  2/334 (0.60%)  2 5/334 (1.50%)  5 5/332 (1.51%)  5
Hypoxia  1  1/334 (0.30%)  1 1/334 (0.30%)  1 1/332 (0.30%)  1
Interstitial Lung Disease  1  1/334 (0.30%)  1 1/334 (0.30%)  1 0/332 (0.00%)  0
Laryngeal Haemorrhage  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Lung Consolidation  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Lung Disorder  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Paranasal Cyst  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Pleural Effusion  1  0/334 (0.00%)  0 2/334 (0.60%)  2 1/332 (0.30%)  3
Pneumonia Aspiration  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Pneumonitis  1  2/334 (0.60%)  2 10/334 (2.99%)  10 11/332 (3.31%)  11
Pneumothorax  1  3/334 (0.90%)  3 3/334 (0.90%)  3 2/332 (0.60%)  2
Pneumothorax Spontaneous  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Pulmonary Embolism  1  3/334 (0.90%)  3 3/334 (0.90%)  3 7/332 (2.11%)  7
Pulmonary Oedema  1  0/334 (0.00%)  0 0/334 (0.00%)  0 2/332 (0.60%)  2
Respiratory Failure  1  3/334 (0.90%)  3 2/334 (0.60%)  2 3/332 (0.90%)  4
Skin and subcutaneous tissue disorders       
Dermatitis Acneiform  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Erythema Multiforme  1  0/334 (0.00%)  0 0/334 (0.00%)  0 1/332 (0.30%)  1
Rash  1  0/334 (0.00%)  0 1/334 (0.30%)  1 1/332 (0.30%)  1
Surgical and medical procedures       
Therapeutic Embolisation  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Vascular disorders       
Deep Vein Thrombosis  1  1/334 (0.30%)  1 0/334 (0.00%)  0 1/332 (0.30%)  1
Embolism  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Haemodynamic Instability  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Hypotension  1  0/334 (0.00%)  0 1/334 (0.30%)  1 1/332 (0.30%)  1
Orthostatic Hypotension  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Peripheral Arterial Occlusive Disease  1  0/334 (0.00%)  0 1/334 (0.30%)  1 0/332 (0.00%)  0
Superior Vena Cava Syndrome  1  0/334 (0.00%)  0 2/334 (0.60%)  2 0/332 (0.00%)  0
1
Term from vocabulary, MeDRA Version 21.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   315/334 (94.31%)      325/334 (97.31%)      315/332 (94.88%)    
Blood and lymphatic system disorders       
Anaemia  1  193/334 (57.78%)  244 186/334 (55.69%)  250 128/332 (38.55%)  154
Leukopenia  1  34/334 (10.18%)  54 42/334 (12.57%)  86 8/332 (2.41%)  8
Neutropenia  1  122/334 (36.53%)  212 121/334 (36.23%)  260 42/332 (12.65%)  59
Thrombocytopenia  1  92/334 (27.54%)  170 90/334 (26.95%)  161 46/332 (13.86%)  66
Endocrine disorders       
Hypothyroidism  1  2/334 (0.60%)  2 31/334 (9.28%)  36 25/332 (7.53%)  26
Gastrointestinal disorders       
Abdominal Pain Upper  1  17/334 (5.09%)  17 12/334 (3.59%)  15 12/332 (3.61%)  15
Constipation  1  72/334 (21.56%)  84 101/334 (30.24%)  124 75/332 (22.59%)  93
Diarrhoea  1  77/334 (23.05%)  107 88/334 (26.35%)  128 93/332 (28.01%)  114
Nausea  1  96/334 (28.74%)  136 129/334 (38.62%)  197 93/332 (28.01%)  133
Stomatitis  1  15/334 (4.49%)  17 22/334 (6.59%)  26 19/332 (5.72%)  22
Vomitting  1  48/334 (14.37%)  59 63/334 (18.86%)  78 49/332 (14.76%)  62
General disorders       
Asthenia  1  66/334 (19.76%)  85 58/334 (17.37%)  79 77/332 (23.19%)  99
Chest Pain  1  18/334 (5.39%)  19 24/334 (7.19%)  29 27/332 (8.13%)  29
Fatigue  1  88/334 (26.35%)  101 103/334 (30.84%)  127 95/332 (28.61%)  109
Malaise  1  16/334 (4.79%)  24 17/334 (5.09%)  25 10/332 (3.01%)  14
Mucosal Inflammation  1  9/334 (2.69%)  11 16/334 (4.79%)  23 17/332 (5.12%)  17
Oedema Peripheral  1  22/334 (6.59%)  25 26/334 (7.78%)  31 22/332 (6.63%)  27
Pyrexia  1  34/334 (10.18%)  42 44/334 (13.17%)  65 44/332 (13.25%)  63
Infections and infestations       
Nasopharyngitis  1  8/334 (2.40%)  10 17/334 (5.09%)  18 17/332 (5.12%)  27
Pneumonia  1  13/334 (3.89%)  14 17/334 (5.09%)  18 14/332 (4.22%)  14
Respiratory Tract Infection  1  6/334 (1.80%)  6 9/334 (2.69%)  13 22/332 (6.63%)  34
Upper Respiratory Tract Infection  1  6/334 (1.80%)  6 17/334 (5.09%)  23 15/332 (4.52%)  23
Urinary Tract Infection  1  14/334 (4.19%)  18 25/334 (7.49%)  39 16/332 (4.82%)  21
Investigations       
Alanine Aminotransferase Increased  1  18/334 (5.39%)  23 40/334 (11.98%)  61 33/332 (9.94%)  53
Aspartate Aminotransferase Increased  1  17/334 (5.09%)  27 34/334 (10.18%)  60 30/332 (9.04%)  50
Blood Alkaline Phosphatase Increased  1  8/334 (2.40%)  8 13/334 (3.89%)  14 25/332 (7.53%)  33
Blood Creatinine Increased  1  3/334 (0.90%)  4 23/334 (6.89%)  26 13/332 (3.92%)  13
Neutrophil Count Decreased  1  65/334 (19.46%)  145 60/334 (17.96%)  132 17/332 (5.12%)  24
Platelet Count Decreased  1  59/334 (17.66%)  110 59/334 (17.66%)  125 40/332 (12.05%)  64
Weight Decreased  1  14/334 (4.19%)  14 29/334 (8.68%)  34 20/332 (6.02%)  21
White Blood Cell Count Decreased  1  36/334 (10.78%)  68 32/334 (9.58%)  64 12/332 (3.61%)  19
Metabolism and nutrition disorders       
Decreased Appetite  1  84/334 (25.15%)  98 83/334 (24.85%)  107 92/332 (27.71%)  106
Dehydration  1  11/334 (3.29%)  15 23/334 (6.89%)  33 20/332 (6.02%)  30
Hyperglycaemia  1  17/334 (5.09%)  19 18/334 (5.39%)  24 25/332 (7.53%)  28
Hypokalaemia  1  23/334 (6.89%)  28 28/334 (8.38%)  35 24/332 (7.23%)  30
Hypomagnesaemia  1  38/334 (11.38%)  56 53/334 (15.87%)  78 35/332 (10.54%)  40
Musculoskeletal and connective tissue disorders       
Arthralgia  1  22/334 (6.59%)  25 38/334 (11.38%)  51 61/332 (18.37%)  80
Back Pain  1  16/334 (4.79%)  17 36/334 (10.78%)  40 31/332 (9.34%)  35
Bone Pain  1  3/334 (0.90%)  3 9/334 (2.69%)  11 22/332 (6.63%)  34
Musculoskeletal Pain  1  13/334 (3.89%)  16 21/334 (6.29%)  28 26/332 (7.83%)  32
Myalgia  1  19/334 (5.69%)  24 22/334 (6.59%)  23 43/332 (12.95%)  62
Pain in Extremity  1  17/334 (5.09%)  17 31/334 (9.28%)  34 35/332 (10.54%)  46
Nervous system disorders       
Dizziness  1  32/334 (9.58%)  41 31/334 (9.28%)  36 31/332 (9.34%)  33
Dysgeusia  1  30/334 (8.98%)  31 31/334 (9.28%)  35 16/332 (4.82%)  16
Headache  1  18/334 (5.39%)  26 30/334 (8.98%)  35 37/332 (11.14%)  43
Neuropathy Peripherial  1  35/334 (10.48%)  38 34/334 (10.18%)  39 66/332 (19.88%)  73
Paraesthesia  1  15/334 (4.49%)  16 16/334 (4.79%)  17 26/332 (7.83%)  31
Peripheral Sensory Neuropathy  1  30/334 (8.98%)  35 48/334 (14.37%)  54 55/332 (16.57%)  68
Psychiatric disorders       
Insomnia  1  27/334 (8.08%)  28 30/334 (8.98%)  34 29/332 (8.73%)  31
Respiratory, thoracic and mediastinal disorders       
Cough  1  51/334 (15.27%)  61 59/334 (17.66%)  74 59/332 (17.77%)  67
Dysphonia  1  11/334 (3.29%)  11 18/334 (5.39%)  18 14/332 (4.22%)  14
Dyspnoea  1  57/334 (17.07%)  65 66/334 (19.76%)  94 61/332 (18.37%)  72
Epistaxis  1  37/334 (11.08%)  43 34/334 (10.18%)  37 8/332 (2.41%)  9
Haemoptysis  1  18/334 (5.39%)  27 18/334 (5.39%)  28 18/332 (5.42%)  20
Skin and subcutaneous tissue disorders       
Alopecia  1  102/334 (30.54%)  103 113/334 (33.83%)  113 130/332 (39.16%)  134
Dry Skin  1  5/334 (1.50%)  5 17/334 (5.09%)  18 13/332 (3.92%)  14
Pruritus  1  12/334 (3.59%)  13 20/334 (5.99%)  29 32/332 (9.64%)  42
Rash  1  18/334 (5.39%)  19 42/334 (12.57%)  47 41/332 (12.35%)  53
Vascular disorders       
Hypotension  1  11/334 (3.29%)  17 18/334 (5.39%)  25 22/332 (6.63%)  25
1
Term from vocabulary, MeDRA Version 21.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02367794    
Other Study ID Numbers: GO29437
2014-003208-59 ( EudraCT Number )
First Submitted: February 13, 2015
First Posted: February 20, 2015
Results First Submitted: September 25, 2019
Results First Posted: November 12, 2019
Last Update Posted: April 13, 2021