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A Global Study to Assess the Effects of MEDI4736 Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02125461
Recruitment Status : Active, not recruiting
First Posted : April 29, 2014
Results First Posted : January 30, 2019
Last Update Posted : September 22, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Non-Small Cell Lung Cancer
Interventions Drug: MEDI4736
Other: PLACEBO
Enrollment 713
Recruitment Details Patients were randomized between 09 May 2014 and 22 Apr 2016 in 235 study centers across 26 countries. 2 interim analysis have been conducted for this study with data cut-off (DCO) dates as indicated. Results are reported for analysis of progression-free survival (PFS) (DCO: 13 Feb 2017) and analysis of overall survival (OS) (DCO: 22 Mar 2018).
Pre-assignment Details Eligible patients with locally advanced, unresectable Stage III non-small cell lung cancer (NSCLC) were randomized in a 2:1 ratio to receive either durvalumab (MEDI4736) 10 milligrams (mg) / kilogram (kg) every 2 weeks (Q2W) or placebo.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months. Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Period Title: Overall Study
Started [1] 476 237
Full Analysis Set (FAS) 476 237
Receieved Treatment 473 236
Safety Analysis Set 475 234
Completed 12 Months of Treatment 232 82
Completed [2] 273 108
Not Completed 203 129
Reason Not Completed
Withdrawal by Subject             22             14
Lost to Follow-up             1             0
Death             180             115
[1]
Randomized
[2]
Ongoing study at OS analysis DCO
Arm/Group Title Durvalumab (MEDI4736) Placebo Total
Hide Arm/Group Description Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months. Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months. Total of all reporting groups
Overall Number of Baseline Participants 476 237 713
Hide Baseline Analysis Population Description
Baseline analysis was based on the FAS consisting of all randomized patients.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 476 participants 237 participants 713 participants
63.0  (8.66) 62.6  (9.64) 62.9  (8.99)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 476 participants 237 participants 713 participants
Female
142
  29.8%
71
  30.0%
213
  29.9%
Male
334
  70.2%
166
  70.0%
500
  70.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 476 participants 237 participants 713 participants
White
337
  70.8%
157
  66.2%
494
  69.3%
Black or African American
12
   2.5%
2
   0.8%
14
   2.0%
Asian
120
  25.2%
72
  30.4%
192
  26.9%
Native Hawaiian or Pacific Islander
1
   0.2%
1
   0.4%
2
   0.3%
American Indian or Alaska Native
4
   0.8%
5
   2.1%
9
   1.3%
Other
1
   0.2%
0
   0.0%
1
   0.1%
Missing
1
   0.2%
0
   0.0%
1
   0.1%
Smoking History  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 476 participants 237 participants 713 participants
Non-smoker
43
   9.0%
21
   8.9%
64
   9.0%
Ex-smoker
354
  74.4%
178
  75.1%
532
  74.6%
Current smoker
79
  16.6%
38
  16.0%
117
  16.4%
1.Primary Outcome
Title Progression Free Survival Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Hide Description PFS was defined as the time from randomization until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression). Progression was defined using RECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PFS was calculated using the Kaplan-Meier technique.
Time Frame Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized patients, analyzed on an intent-to-treat (ITT) basis.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 476 237
Median (95% Confidence Interval)
Unit of Measure: Months
16.8
(13.0 to 18.1)
5.6
(4.6 to 7.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Durvalumab (MEDI4736), Placebo
Comments Analysis performed using a stratified log rank test adjusting for age at randomization (<65 vs ≥65), sex (male vs female), and smoking history (smoker vs non-smoker) with ties handled using the Breslow approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.42 to 0.65
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival
Hide Description OS was defined as the time from the date of randomization until death due to any cause. OS was calculated using the Kaplan-Meier technique.
Time Frame From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized patients, analyzed on an ITT basis.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 476 237
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(34.7 to NA)
28.7 [2] 
(22.9 to NA)
[1]
The median and upper limit of 95% confidence interval (CI) could not be calculated as they were not reached.
[2]
Upper limit of 95% CI could not be calculated as it was not reached.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Durvalumab (MEDI4736), Placebo
Comments Analysis performed using a stratified log rank test adjusting for age at randomization (<65 vs ≥65), sex (male vs female), and smoking history (smoker vs non-smoker) with ties handled using the Breslow approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00251
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.53 to 0.87
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Objective Response Rate (ORR) Based on BICR Assesments According to RECIST 1.1
Hide Description ORR was defined as the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) per RECIST 1.1 for target lesions: CR: Disappearance of all target lesions; PR: >=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.
Time Frame Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (which included all randomized patients) with measureable disease at baseline, analyzed on an ITT basis.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 443 213
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
30.0
(25.79 to 34.53)
17.8
(12.95 to 23.65)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Durvalumab (MEDI4736), Placebo
Comments Analysis performed using Fisher's exact test with mid p-value modification by subtracting half of the probability of the observed table from Fisher's p-value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Duration of Response (DoR) Based on BICR Assessments According to RECIST 1.1
Hide Description DoR was defined as the time from date for first documented response of CR or PR until the first documented response of progression per RECIST 1.1 or death in the absence of progression. DoR was calculated using the Kaplan-Meier technique.
Time Frame Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized patients, analyzed on an ITT basis. Only patients with an objective response were included in the analysis.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 133 38
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(27.4 to NA)
18.4
(6.7 to 24.5)
[1]
The median and upper limit of 95% CI could not be calculated as they were not reached.
5.Secondary Outcome
Title Proportion of Patients Alive and Progression Free at 12 Months From (APF12) Based on BICR Assessments According to RECIST 1.1
Hide Description APF12 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 12 months after randomization per Kaplan-Meier estimate of PFS at 12 months.
Time Frame Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized patients, analyzed on an ITT basis.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 476 237
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
55.9
(51.0 to 60.4)
35.3
(29.0 to 41.7)
6.Secondary Outcome
Title Proportion of Patients Alive and Progression Free at 18 Months From (APF18) Based on BICR Assessments According to RECIST 1.1
Hide Description APF18 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 18 months after randomization per the Kaplan-Meier estimate of PFS at 18 months.
Time Frame Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized patients, analyzed on an ITT basis.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 476 237
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
44.2
(37.7 to 50.5)
27.0
(19.9 to 34.5)
7.Secondary Outcome
Title Time to Death or Distant Metastasis (TTDM) Based on BICR Assessments According to RECIST 1.1
Hide Description TTDM was defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis was defined as any new lesion that was outside of the radiation field according to RECIST 1.1 or proven by biopsy. TTDM was calculated using the Kaplan-Meier technique.
Time Frame Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized patients, analyzed on an ITT basis.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 476 237
Median (95% Confidence Interval)
Unit of Measure: Months
28.3
(24.0 to 34.9)
16.2
(12.5 to 21.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Durvalumab (MEDI4736), Placebo
Comments Analysis performed using a stratified log rank test adjusting for age at randomization (<65 vs ≥65), sex (male vs female), and smoking history (smoker vs non-smoker) with ties handled using the Breslow approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.41 to 0.68
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Patients Alive at 24 Months (OS24)
Hide Description OS24 was defined as the percentage of patients who were alive at 24 months after randomization per the Kaplan-Meier estimate of OS at 24 months.
Time Frame From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized patients, analyzed on an ITT basis.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 476 237
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
66.3
(61.7 to 70.4)
55.6
(48.9 to 61.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Durvalumab (MEDI4736), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments P-value generated based on z-test where z-test statistic is the ratio of the log-transformed ratio of the cumulative hazards in the two treatment arms divided by the square root of the variance.
Method z-test
Comments The variance was estimated using the delta method and Greenwood's formula.
9.Secondary Outcome
Title Time to Second Progression or Death (PFS2)
Hide Description PFS2 was defined as the time from randomization to the time of the second progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could have involved any of the following: objective radiological, symptomatic progression, or death. RECIST assessments were not collected for assessment of PFS2. PFS2 was calculated using the Kaplan-Meier technique.
Time Frame Following confirmed progression, patients were assessed every ~12 weeks until second disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized patients, analyzed on an ITT basis.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 476 237
Median (95% Confidence Interval)
Unit of Measure: Months
28.3
(25.1 to 34.7)
17.1
(14.5 to 20.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Durvalumab (MEDI4736), Placebo
Comments Analysis performed using a stratified log rank test adjusting for age at randomization (<65 vs ≥65), sex (male vs female), and smoking history (smoker vs non-smoker) with ties handled using the Breslow approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.46 to 0.73
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Time to Deterioration of Global Health Status / Health-Related Quality of Life (HRQoL), Assessed Using European Organization for Research and Treatment of Cancer 30-Item Core Quality of Life Questionnaire (EORTC QLQ-C30)
Hide Description Global health status/HRQoL was assessed using the EORTC QLQ-C30 global QoL scale which includes 2 items from the QLQ-C30: "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall QoL during the past week?" (Item 30). Scores from 0 to 100 were derived for each item with higher scores indicating a better health status. Time to deterioration for global health status/HRQoL was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in global health status/HRQoL from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful deterioration. Time to deterioration was calculated using the Kaplan-Meier technique.
Time Frame At baseline, every 4 weeks for first 8 weeks, then every ~8 weeks until 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized patients, analyzed on an ITT basis. Only patients with baseline scores ≥ 10 were included in the analysis.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 476 237
Median (95% Confidence Interval)
Unit of Measure: Months
7.4
(5.5 to 9.3)
5.7
(4.2 to 10.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Durvalumab (MEDI4736), Placebo
Comments The hazard ratio and CI were estimated from a stratified Cox proportional hazards model with the Breslow method to control for ties, the stratification factors age at randomization (<65 vs ≥65), sex (male vs female) and smoking history (smoker vs non-smoker) in the strata statement, and the CI calculated using a profile likelihood approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.664
Comments Analysis performed using a stratified log rank test adjusting for age at randomization (<65 vs ≥65), sex (male vs female), and smoking history (smoker vs non-smoker) with ties handled using the Breslow approach.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.77 to 1.18
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Time to Deterioration of Primary Patient-Reported Outcome (PRO) Symptoms, Assessed Using European Organization for Research and Treatment of Cancer QoL Lung Cancer Module (EORTC QLQ-LC13)
Hide Description The EORTC QLQ-LC13 is a lung cancer specific module from the EORTC comprising 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, chest pain, arm/shoulder pain, and other pain), treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication. Scores from 0 to 100 were derived for each symptom item with higher scores representing greater symptom severity. Time to symptom deterioration was defined as time from randomization until the date of first clinically meaningful symptom deterioration (an increase in the score from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful symptom deterioration. Results are presented for time to deterioration in the following PRO endpoints identified as primary for EORTC QLQ-LC13: dyspnea, cough, hemoptysis and chest pain. Time to deterioration was calculated using the Kaplan-Meier technique.
Time Frame At baseline, every 4 weeks for first 8 weeks, then every ~8 weeks until 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized patients, analyzed on an ITT basis. Only patients with baseline scores ≤ 90 were included in the analysis.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 476 237
Median (95% Confidence Interval)
Unit of Measure: Months
Dyspnea Number Analyzed 467 participants 230 participants
2.8
(1.9 to 3.7)
3.7
(2.3 to 4.1)
Cough Number Analyzed 442 participants 216 participants
5.6
(4.5 to 7.3)
5.6
(3.7 to 6.0)
Hemoptysis Number Analyzed 472 participants 232 participants
NA [1] 
(NA to NA)
29.6 [2] 
(21.2 to NA)
Chest pain Number Analyzed 463 participants 229 participants
11.1
(7.4 to 18.6)
8.3
(5.6 to 13.8)
[1]
The median and 95% CIs could not be calculated as they were not reached.
[2]
Upper limit of 95% CI could not be calculated as it was not reached.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Durvalumab (MEDI4736), Placebo
Comments Treatment comparison for dyspnea. The hazard ratio and CI were estimated from a stratified Cox proportional hazards model with the Breslow method to control for ties, the stratification factors age at randomization (<65 vs ≥65), sex (male vs female) and smoking history (smoker vs non-smoker) in the strata statement, and the CI calculated using a profile likelihood approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.522
Comments Analysis performed using a stratified log rank test adjusting for age at randomization (<65 vs ≥65), sex (male vs female), and smoking history (smoker vs non-smoker) with ties handled using the Breslow approach.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.88 to 1.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Durvalumab (MEDI4736), Placebo
Comments Treatment comparison for cough. The hazard ratio and CI were estimated from a stratified Cox proportional hazards model with the Breslow method to control for ties, the stratification factors age at randomization (<65 vs ≥65), sex (male vs female) and smoking history (smoker vs non-smoker) in the strata statement, and the CI calculated using a profile likelihood approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.380
Comments Analysis performed using a stratified log rank test adjusting for age at randomization (<65 vs ≥65), sex (male vs female), and smoking history (smoker vs non-smoker) with ties handled using the Breslow approach.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.74 to 1.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Durvalumab (MEDI4736), Placebo
Comments Treatment comparison for hemoptysis. The hazard ratio and CI were estimated from a stratified Cox proportional hazards model with the Breslow method to control for ties, the stratification factors age at randomization (<65 vs ≥65), sex (male vs female) and smoking history (smoker vs non-smoker) in the strata statement, and the CI calculated using a profile likelihood approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments Analysis performed using a stratified log rank test adjusting for age at randomization (<65 vs ≥65), sex (male vs female), and smoking history (smoker vs non-smoker) with ties handled using the Breslow approach.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.56 to 1.00
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Durvalumab (MEDI4736), Placebo
Comments Treatment comparison for chest pain. The hazard ratio and CI were estimated from a stratified Cox proportional hazards model with the Breslow method to control for ties, the stratification factors age at randomization (<65 vs ≥65), sex (male vs female) and smoking history (smoker vs non-smoker) in the strata statement, and the CI calculated using a profile likelihood approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.626
Comments Analysis performed using a stratified log rank test adjusting for age at randomization (<65 vs ≥65), sex (male vs female), and smoking history (smoker vs non-smoker) with ties handled using the Breslow approach.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.75 to 1.19
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations
Hide Description To evaluate PK, blood samples were collected pre-dose and post-dose and trough and peak serum concentrations of durvalumab, respectively, were determined. Pre-dose samples were taken within 60 minutes before infusion and post-dose samples were taken within 10 minutes after the end of infusion.
Time Frame Samples were collected pre-dose on Day 1 (Week 0), Week 8, Week 24 and Week 48, and post-dose on Day 1 (Week 0) and Week 24. Analysis performed at 22 Mar 2018 DCO.
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all patients who received at least 1 dose of durvalumab per the protocol, for whom any post-dose data were available, and who did not violate or deviate from the protocol in ways that would significantly affect the PK analyses.
Arm/Group Title Durvalumab (MEDI4736)
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Overall Number of Participants Analyzed 473
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Micrograms per milliliter
Week 0: peak concentration Number Analyzed 385 participants
191.00
(72.4%)
Week 8: trough concentration Number Analyzed 289 participants
120.00
(62.2%)
Week 24: trough concentration Number Analyzed 225 participants
177.00
(47.9%)
Week 24: peak concentration Number Analyzed 207 participants
373.00
(43.6%)
Week 48: trough concentration Number Analyzed 213 participants
186.00
(67.4%)
13.Secondary Outcome
Title Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab
Hide Description ADA positive post-baseline only was also referred to as treatment-induced ADA positive. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted by ≥4-fold following drug administration. Persistently positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Confirmed ADA positive samples were subsequently tested in a neutralizing antibody assay.
Time Frame Samples were collected pre-dose on Day 1 (Week 0), Week 8, Week 24 and Week 48. Analysis performed at 22 Mar 2018 DCO.
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Hide Analysis Population Description
ADA evaluable population included patients who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA results.
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description:
Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months.
Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
Overall Number of Participants Analyzed 416 204
Measure Type: Count of Participants
Unit of Measure: Participants
ADA positive at any visit
19
   4.6%
10
   4.9%
ADA positive post-baseline only
8
   1.9%
5
   2.5%
Treatment-boosted ADA positive
0
   0.0%
0
   0.0%
ADA positive at baseline and post-baseline
2
   0.5%
2
   1.0%
ADA positive at baseline only
9
   2.2%
3
   1.5%
ADA persistently positive
5
   1.2%
5
   2.5%
ADA transient positive
5
   1.2%
2
   1.0%
Neutralizing antibodies positive at any visit
3
   0.7%
0
   0.0%
Time Frame Serious and Other (non-serious) treatment-emergent adverse event (TEAE) data was observed up until 90 days following discontinuation of durvalumab/placebo or until the initiation of the first subsequent therapy (whichever occurred first). Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Adverse Event Reporting Description All-cause mortality is defined as death due to any cause (including disease progression) and is reported for the FAS. TEAE data is reported for the safety analysis set. 473 and 236 patients in the durvalumab and placebo groups, respectively, received treatment but 2 patients randomized to the placebo group inadvertently received 1 dose of durvalumab and are included in the durvalumab group of the safety analysis set.
 
Arm/Group Title Durvalumab (MEDI4736) Placebo
Hide Arm/Group Description Patients in the durvalumab (MEDI4736) monotherapy group were to receive durvalumab 10 mg/kg Q2W via intravenous infusion for up to 12 months. Patients in the placebo group were to receive matching placebo for intravenous infusion Q2W for up to 12 months.
All-Cause Mortality
Durvalumab (MEDI4736) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   183/476 (38.45%)      116/237 (48.95%)    
Hide Serious Adverse Events
Durvalumab (MEDI4736) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   138/475 (29.05%)      54/234 (23.08%)    
Blood and lymphatic system disorders     
Anaemia  1  2/475 (0.42%)  3 0/234 (0.00%)  0
Thrombocytopenia  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Cardiac disorders     
Acute coronary syndrome  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Acute myocardial infarction  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Angina pectoris  1  2/475 (0.42%)  3 0/234 (0.00%)  0
Arrhythmia supraventricular  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Arteriospasm coronary  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Atrial fibrillation  1  5/475 (1.05%)  7 0/234 (0.00%)  0
Atrioventricular block complete  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Cardiac arrest  1  2/475 (0.42%)  2 1/234 (0.43%)  1
Cardiac disorder  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Cardiac failure  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Cardiac failure congestive  1  4/475 (0.84%)  5 0/234 (0.00%)  0
Cardiogenic shock  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Cardiomyopathy  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Cardiopulmonary failure  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Eosinophilic myocarditis  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Myocardial infarction  1  3/475 (0.63%)  3 0/234 (0.00%)  0
Myocardial ischaemia  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Pericardial effusion  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Right ventricular failure  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Ventricular tachycardia  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Bradycardia  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Eye disorders     
Macular hole  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Gastrointestinal disorders     
Abdominal pain lower  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Abdominal pain upper  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Diarrhoea  1  1/475 (0.21%)  1 2/234 (0.85%)  2
Diverticulum  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Enteritis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Gastric ulcer  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Haemorrhoidal haemorrhage  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Inguinal hernia  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Vomiting  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Haemorrhoids  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Intestinal obstruction  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Nausea  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Oesophageal stenosis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Oesophagitis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
General disorders     
Influenza like illness  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Mucosal inflammation  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Asthenia  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Death  1  1/475 (0.21%)  1 1/234 (0.43%)  1
Fatigue  1  0/475 (0.00%)  0 2/234 (0.85%)  2
Infusion site extravasation  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Non-cardiac chest pain  1  1/475 (0.21%)  1 1/234 (0.43%)  1
Pyrexia  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Immune system disorders     
Sarcoidosis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Infections and infestations     
Lung abscess  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Pneumocystis jirovecii pneumonia  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Pneumonia  1  27/475 (5.68%)  33 12/234 (5.13%)  14
Pneumonia adenoviral  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Pneumonia necrotising  1  0/475 (0.00%)  0 2/234 (0.85%)  3
Pneumonia pneumococcal  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Sepsis  1  4/475 (0.84%)  4 2/234 (0.85%)  2
Septic shock  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Sinusitis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Chest wall abscess  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Endotoxaemia  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Gastroenteritis  1  1/475 (0.21%)  1 1/234 (0.43%)  1
Haemophilus infection  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Herpes zoster  1  3/475 (0.63%)  3 0/234 (0.00%)  0
Influenza  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Lower respiratory tract infection bacterial  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Lung infection  1  6/475 (1.26%)  6 2/234 (0.85%)  2
Necrotising fasciitis  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Peritonitis  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Pneumonia bacterial  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Pneumonia haemophilus  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Pneumonia streptococcal  1  1/475 (0.21%)  1 1/234 (0.43%)  1
Skin infection  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Upper respiratory tract infection  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Viral upper respiratory tract infection  1  1/475 (0.21%)  1 0/234 (0.00%)  0
West Nile viral infection  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Injury, poisoning and procedural complications     
Fall  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Radiation oesophagitis  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Femoral neck fracture  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Infusion related reaction  1  1/475 (0.21%)  5 0/234 (0.00%)  0
Post procedural fistula  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Radiation pneumonitis  1  17/475 (3.58%)  17 4/234 (1.71%)  5
Spinal compression fracture  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Spinal fracture  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Traumatic intracranial haemorrhage  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Investigations     
Brain natriuretic peptide increased  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Ejection fraction decreased  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Myocardial necrosis marker increased  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Metabolism and nutrition disorders     
Iron overload  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Decreased appetite  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Hyperkalaemia  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Type 1 diabetes mellitus  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Flank pain  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Musculoskeletal pain  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Intervertebral disc degeneration  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Myopathy  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Polymyalgia rheumatica  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Giant cell tumour of tendon sheath  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Prostate cancer  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Bladder cancer  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Cancer pain  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Malignant melanoma  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Papillary thyroid cancer  1  1/475 (0.21%)  1 1/234 (0.43%)  1
Small intestine carcinoma  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Squamous cell carcinoma  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Squamous cell carcinoma of skin  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Nervous system disorders     
Carotid artery stenosis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Cerebrovascular accident  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Metabolic encephalopathy  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Syncope  1  1/475 (0.21%)  1 1/234 (0.43%)  1
Psychiatric disorders     
Adjustment disorder with mixed anxiety and depressed mood  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Alcohol withdrawal syndrome  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Renal and urinary disorders     
Glomerulonephritis membranous  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Acute kidney injury  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Acute prerenal failure  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Nephrolithiasis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Renal tubular acidosis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Reproductive system and breast disorders     
Calculus prostatic  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Bronchial obstruction  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Haemoptysis  1  2/475 (0.42%)  2 1/234 (0.43%)  1
Acquired tracheo-oesophageal fistula  1  1/475 (0.21%)  1 1/234 (0.43%)  1
Acute interstitial pneumonitis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Acute respiratory failure  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Bronchopleural fistula  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Chronic obstructive pulmonary disease  1  5/475 (1.05%)  8 0/234 (0.00%)  0
Dyspnoea  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Emphysema  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Hypoxia  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Interstitial lung disease  1  0/475 (0.00%)  0 2/234 (0.85%)  2
Pleural effusion  1  1/475 (0.21%)  2 0/234 (0.00%)  0
Pneumonia aspiration  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Pneumonitis  1  17/475 (3.58%)  18 7/234 (2.99%)  8
Pneumothorax  1  2/475 (0.42%)  2 1/234 (0.43%)  1
Pulmonary embolism  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Respiratory distress  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Respiratory failure  1  2/475 (0.42%)  2 0/234 (0.00%)  0
Vascular disorders     
Aortic dissection  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Hypertension  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Hypotension  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Jugular vein thrombosis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Peripheral ischaemia  1  0/475 (0.00%)  0 1/234 (0.43%)  1
Shock  1  1/475 (0.21%)  1 0/234 (0.00%)  0
Vena cava thrombosis  1  1/475 (0.21%)  1 0/234 (0.00%)  0
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Durvalumab (MEDI4736) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   436/475 (91.79%)      211/234 (90.17%)    
Blood and lymphatic system disorders     
Anaemia  1  35/475 (7.37%)  39 26/234 (11.11%)  32
Endocrine disorders     
Hyperthyroidism  1  35/475 (7.37%)  39 4/234 (1.71%)  4
Hypothyroidism  1  55/475 (11.58%)  63 4/234 (1.71%)  4
Gastrointestinal disorders     
Constipation  1  56/475 (11.79%)  58 20/234 (8.55%)  27
Diarrhoea  1  87/475 (18.32%)  135 46/234 (19.66%)  56
Vomiting  1  36/475 (7.58%)  45 19/234 (8.12%)  25
Nausea  1  68/475 (14.32%)  88 31/234 (13.25%)  43
General disorders     
Asthenia  1  51/475 (10.74%)  73 31/234 (13.25%)  50
Fatigue  1  114/475 (24.00%)  130 47/234 (20.09%)  52
Non-cardiac chest pain  1  35/475 (7.37%)  39 21/234 (8.97%)  22
Oedema peripheral  1  37/475 (7.79%)  41 9/234 (3.85%)  10
Pyrexia  1  70/475 (14.74%)  92 22/234 (9.40%)  23
Infections and infestations     
Upper respiratory tract infection  1  57/475 (12.00%)  69 24/234 (10.26%)  30
Bronchitis  1  33/475 (6.95%)  44 19/234 (8.12%)  22
Nasopharyngitis  1  42/475 (8.84%)  49 14/234 (5.98%)  18
Pneumonia  1  39/475 (8.21%)  45 7/234 (2.99%)  9
Urinary tract infection  1  28/475 (5.89%)  42 13/234 (5.56%)  13
Injury, poisoning and procedural complications     
Radiation pneumonitis  1  80/475 (16.84%)  84 33/234 (14.10%)  33
Metabolism and nutrition disorders     
Decreased appetite  1  68/475 (14.32%)  83 29/234 (12.39%)  32
Hypokalaemia  1  24/475 (5.05%)  33 12/234 (5.13%)  18
Musculoskeletal and connective tissue disorders     
Arthralgia  1  59/475 (12.42%)  74 26/234 (11.11%)  28
Back pain  1  50/475 (10.53%)  55 27/234 (11.54%)  31
Musculoskeletal chest pain  1  25/475 (5.26%)  27 18/234 (7.69%)  21
Musculoskeletal pain  1  39/475 (8.21%)  44 23/234 (9.83%)  27
Myalgia  1  38/475 (8.00%)  41 10/234 (4.27%)  13
Pain in extremity  1  32/475 (6.74%)  36 14/234 (5.98%)  14
Nervous system disorders     
Dizziness  1  33/475 (6.95%)  36 22/234 (9.40%)  25
Headache  1  52/475 (10.95%)  58 21/234 (8.97%)  23
Paraesthesia  1  22/475 (4.63%)  24 12/234 (5.13%)  13
Psychiatric disorders     
Insomnia  1  45/475 (9.47%)  47 17/234 (7.26%)  18
Respiratory, thoracic and mediastinal disorders     
Cough  1  167/475 (35.16%)  216 59/234 (25.21%)  75
Dyspnoea  1  105/475 (22.11%)  132 56/234 (23.93%)  66
Pneumonitis  1  44/475 (9.26%)  46 11/234 (4.70%)  11
Productive cough  1  46/475 (9.68%)  53 18/234 (7.69%)  25
Skin and subcutaneous tissue disorders     
Dry skin  1  37/475 (7.79%)  38 12/234 (5.13%)  12
Pruritus  1  59/475 (12.42%)  69 12/234 (5.13%)  14
Rash  1  58/475 (12.21%)  69 18/234 (7.69%)  22
Vascular disorders     
Hypertension  1  26/475 (5.47%)  29 8/234 (3.42%)  8
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Results of interim PFS analysis are considered as final PFS analysis; results of interim OS analysis are considered as final OS analysis. Patients will continue to be followed for long-term survival and updated OS analysis will be reported if needed.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
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Name/Title: Global Clinical Lead
Organization: AstraZeneca
Phone: +1 302 885 1180
EMail: ClinicalTrialTransparency@astrazeneca.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02125461    
Other Study ID Numbers: D4191C00001
First Submitted: April 25, 2014
First Posted: April 29, 2014
Results First Submitted: February 13, 2018
Results First Posted: January 30, 2019
Last Update Posted: September 22, 2020