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First-line Esophageal Carcinoma Study With Chemo vs. Chemo Plus Pembrolizumab (MK-3475-590/KEYNOTE-590)

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: NCT03189719
Recruitment Status : Active, not recruiting
First Posted : June 16, 2017
Results First Posted : July 6, 2021
Last Update Posted : January 25, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Esophageal Neoplasms
Interventions Biological: Pembrolizumab
Drug: Placebo
Drug: Cisplatin
Drug: 5-FU
Enrollment 749
Recruitment Details  
Pre-assignment Details 749 participants were randomized 1:1 to receive either pembrolizumab plus standard of care (SOC) chemotherapy, or placebo plus SOC chemotherapy. At the time of the primary analysis data cut-off, 173 participants were ongoing in the study.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) plus standard of care (SOC) chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-fluorouracil (5-FU) 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle. Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Period Title: Overall Study
Started 373 376
Treated 370 370
Completed 0 0
Not Completed 373 376
Reason Not Completed
Death             260             308
Withdrawal by Subject             5             3
Ongoing in Study             108             65
Arm/Group Title Pembrolizumab + SOC Placebo + SOC Total
Hide Arm/Group Description Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle. Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle. Total of all reporting groups
Overall Number of Baseline Participants 373 376 749
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 373 participants 376 participants 749 participants
62.8  (9.8) 62.0  (9.2) 62.4  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 373 participants 376 participants 749 participants
Female
67
  18.0%
57
  15.2%
124
  16.6%
Male
306
  82.0%
319
  84.8%
625
  83.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 373 participants 376 participants 749 participants
Hispanic or Latino
42
  11.3%
57
  15.2%
99
  13.2%
Not Hispanic or Latino
315
  84.5%
296
  78.7%
611
  81.6%
Unknown or Not Reported
16
   4.3%
23
   6.1%
39
   5.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 373 participants 376 participants 749 participants
American Indian or Alaska Native
9
   2.4%
12
   3.2%
21
   2.8%
Asian
201
  53.9%
199
  52.9%
400
  53.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
   1.3%
2
   0.5%
7
   0.9%
White
139
  37.3%
139
  37.0%
278
  37.1%
More than one race
5
   1.3%
9
   2.4%
14
   1.9%
Unknown or Not Reported
14
   3.8%
15
   4.0%
29
   3.9%
Geographic Region   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 373 participants 376 participants 749 participants
Asia
196
  52.5%
197
  52.4%
393
  52.5%
Rest of World
177
  47.5%
179
  47.6%
356
  47.5%
[1]
Measure Description: Participants were stratified according to Geographic Region of enrolling site (Asia versus Rest of World)
Histology   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 373 participants 376 participants 749 participants
Adenocarcinoma
99
  26.5%
102
  27.1%
201
  26.8%
Squamous Cell Carcinoma
274
  73.5%
274
  72.9%
548
  73.2%
[1]
Measure Description: Participants were stratified according to baseline Histology (adenocarcinoma versus squamous cell carcinoma)
Eastern Cooperative Group Performance Status (ECOG PS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 373 participants 376 participants 749 participants
ECOG PS 0
149
  39.9%
150
  39.9%
299
  39.9%
ECOG PS 1
223
  59.8%
225
  59.8%
448
  59.8%
ECOG PS 2
1
   0.3%
1
   0.3%
2
   0.3%
[1]
Measure Description: ECOG PS 0 = Fully active, able to carry on all pre-disease performance without restriction), ECOG PS 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, ECOG PS 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours. Participants were stratified according to baseline ECOG PS (0 versus 1).
1.Primary Outcome
Title Overall Survival (OS) in Participants With Esophageal Squamous Cell Carcinoma (ESCC) Whose Tumors Are Programmed Cell Death-Ligand 1 (PD-L1) Biomarker-Positive (Combined Positive Score [CPS] ≥10)
Hide Description Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the Intent-To-Treat (ITT) population (all randomized) who had ESCC and who were PD-L1 CPS ≥10.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) with ESCC and PD-L1 CPS ≥10 were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 143 143
Median (95% Confidence Interval)
Unit of Measure: Months
13.9
(11.1 to 17.7)
8.8
(7.8 to 10.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments OS in ESCC PD-L1 CPS ≥10 participants of the pembrolizumab + SOC arm was compared to OS in ESCC PD-L1 CPS ≥10 participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Stratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.43 to 0.75
Estimation Comments [Not Specified]
2.Primary Outcome
Title OS in Participants With ESCC
Hide Description Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized) who had ESCC.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) with ESCC were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 274 274
Median (95% Confidence Interval)
Unit of Measure: Months
12.6
(10.2 to 14.3)
9.8
(8.6 to 11.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments OS in ESCC participants of the pembrolizumab + SOC arm was compared to OS in ESCC participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Stratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.60 to 0.88
Estimation Comments [Not Specified]
3.Primary Outcome
Title OS in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
Hide Description Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) who were PD-L1 CPS ≥10 were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 186 197
Median (95% Confidence Interval)
Unit of Measure: Months
13.5
(11.1 to 15.6)
9.4
(8.0 to 10.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments OS in PD-L1 CPS ≥10 participants of the pembrolizumab + SOC arm was compared to OS in PD-L1 CPS ≥10 participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Stratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.49 to 0.78
Estimation Comments [Not Specified]
4.Primary Outcome
Title OS in All Participants
Hide Description Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized).
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 373 376
Median (95% Confidence Interval)
Unit of Measure: Months
12.4
(10.5 to 14.0)
9.8
(8.8 to 10.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments OS in all participants of the pembrolizumab + SOC arm was compared to OS in all participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World), tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma), and ECOG performance status (0 versus 1).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Stratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.62 to 0.86
Estimation Comments [Not Specified]
5.Primary Outcome
Title Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed By Investigator in Participants With ESCC
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who had ESCC.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) with ESCC were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 274 274
Median (95% Confidence Interval)
Unit of Measure: Months
6.3
(6.2 to 6.9)
5.8
(5.0 to 6.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments PFS in ESCC participants of the pembrolizumab + SOC arm was compared to PFS in ESCC participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Stratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.54 to 0.78
Estimation Comments [Not Specified]
6.Primary Outcome
Title PFS Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) who were PD-L1 CPS ≥10 were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 186 197
Median (95% Confidence Interval)
Unit of Measure: Months
7.5
(6.2 to 8.2)
5.5
(4.3 to 6.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments PFS in PD-L1 CPS ≥10 participants of the pembrolizumab + SOC arm was compared to PFS in PD-L1 CPS ≥10 participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Stratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.41 to 0.65
Estimation Comments [Not Specified]
7.Primary Outcome
Title PFS Per RECIST 1.1 As Assessed By Investigator in All Participants
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) who were PD-L1 CPS ≥10 were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 373 376
Median (95% Confidence Interval)
Unit of Measure: Months
6.3
(6.2 to 6.9)
5.8
(5.0 to 6.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments PFS in all participants of the pembrolizumab + SOC arm was compared to PFS in all participants of the placebo + SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by geographic region (Asia versus Rest of the World), tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma), and ECOG performance status (0 versus 1).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Stratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.55 to 0.76
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Objective Response Rate (ORR) Per RECIST 1.1 As Assessed By Investigator in All Participants
Hide Description ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized).
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 373 376
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
45.0
(39.9 to 50.2)
29.3
(24.7 to 34.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments ORR in all participants of the pembrolizumab + SOC arm was compared to ORR in all participants of the placebo + SOC arm based on the Miettinen & Nurminen method stratified by geographic region (Asia versus Rest of the World), tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma), and ECOG performance status (0 versus 1).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method One-sided p-value
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 15.8
Confidence Interval (2-Sided) 95%
9.0 to 22.5
Estimation Comments [Not Specified]
9.Secondary Outcome
Title ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
Hide Description ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who had ESCC and who were PD-L1 CPS ≥10.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) with ESCC and PD-L1 CPS ≥10 were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 143 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
51.0
(42.6 to 59.5)
28.0
(20.8 to 36.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments ORR in ESCC PD-L1 CPS ≥10 participants of the pembrolizumab + SOC arm was compared to ORR in ESCC PD-L1 CPS ≥10 participants of the placebo + SOC arm based on the Miettinen & Nurminen method stratified by geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method One-sided p-value
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 22.8
Confidence Interval (2-Sided) 95%
11.6 to 33.4
Estimation Comments [Not Specified]
10.Secondary Outcome
Title ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC
Hide Description ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who had ESCC.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) with ESCC were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 274 274
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
43.8
(37.8 to 49.9)
31.0
(25.6 to 36.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments ORR in ESCC participants of the pembrolizumab + SOC arm was compared to ORR in ESCC participants of the placebo + SOC arm based on the Miettinen & Nurminen method stratified by geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method One-sided p-value
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 12.8
Confidence Interval (2-Sided) 95%
4.7 to 20.7
Estimation Comments [Not Specified]
11.Secondary Outcome
Title ORR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
Hide Description ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) who were PD-L1 CPS ≥10 were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 186 197
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
51.1
(43.7 to 58.5)
26.9
(20.8 to 33.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments ORR in PD-L1 CPS ≥10 participants of the pembrolizumab + SOC arm was compared to ORR in PD-L1 CPS ≥10 participants of the placebo + SOC arm based on the Miettinen & Nurminen method stratified by geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method One-sided p-value
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 24.0
Confidence Interval (2-Sided) 95%
14.3 to 33.2
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Duration of Response (DOR) Per RECIST 1.1 As Assessed By Investigator in All Participants
Hide Description For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) who demonstrated a confirmed CR or PR were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 168 110
Median (95% Confidence Interval)
Unit of Measure: Months
8.3
(6.4 to 10.4)
6.0
(4.4 to 6.4)
13.Secondary Outcome
Title DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
Hide Description For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and who had ESCC and were PD-L1 CPS ≥10.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) with ESCC and PD-L1 CPS ≥10 who demonstrated a confirmed CR or PR were analyzed were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 73 40
Median (95% Confidence Interval)
Unit of Measure: Months
10.4
(8.0 to 16.2)
4.4
(4.1 to 6.2)
14.Secondary Outcome
Title DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC
Hide Description For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and who had ESCC.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) with ESCC who demonstrated a confirmed CR or PR were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 120 85
Median (95% Confidence Interval)
Unit of Measure: Months
9.1
(6.6 to 12.3)
6.1
(4.4 to 6.4)
15.Secondary Outcome
Title DOR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
Hide Description For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and were PD-L1 CPS ≥10.
Time Frame Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (ITT population) who were PD-L1 CPS ≥10 and who demonstrated a confirmed CR or PR were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 95 53
Median (95% Confidence Interval)
Unit of Measure: Months
10.4
(6.7 to 14.5)
5.6
(4.3 to 6.5)
16.Secondary Outcome
Title Number of Participants With an Adverse Event (AE)
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE was reported for each treatment arm.
Time Frame Up to approximately 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 370 370
Measure Type: Count of Participants
Unit of Measure: Participants
370
 100.0%
368
  99.5%
17.Secondary Outcome
Title Number of Participants Discontinuing Study Treatment Due to an AE
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that discontinued any study drug due to an AE was reported for each treatment arm.
Time Frame Up to approximately 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 370 370
Measure Type: Count of Participants
Unit of Measure: Participants
90
  24.3%
74
  20.0%
18.Secondary Outcome
Title Change From Baseline To Week 18 in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Combined Score in All Participants
Hide Description The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants.
Time Frame Baseline, Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and completed at least 1 EORTC-QLQ-C30 assessment were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 366 363
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a Scale
-1.74
(-4.24 to 0.75)
-1.64
(-4.21 to 0.92)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments Change from baseline to Week 18 in EORTC-QLQ-C30 GHS/QoL combined score was compared between treatment arms based on a constrained longitudinal data analysis (cLDA) model with the EORTC-QLQ-C30 GHS/QoL scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9530
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-3.40 to 3.20
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
Hide Description The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who had ESCC and who were PD-L1 CPS ≥10.
Time Frame Baseline, Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC-QLQ-C30 assessment, who had ESCC, and who were PD-L1 CPS ≥10 were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 142 138
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a Scale
-2.36
(-6.58 to 1.87)
-0.40
(-4.86 to 4.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments Change from baseline to Week 18 in EORTC-QLQ-C30 GHS/QoL combined score was compared between treatment arms based on a cLDA model with the EORTC-QLQ-C30 GHS/QoL scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5053
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -1.95
Confidence Interval (2-Sided) 95%
-7.72 to 3.82
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC
Hide Description The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who had ESCC.
Time Frame Baseline, Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC-QLQ-C30 assessment, and who had ESCC were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 270 264
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a Scale
-2.00
(-4.90 to 0.89)
-1.94
(-4.93 to 1.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments Change from baseline to Week 18 in EORTC-QLQ-C30 GHS/QoL combined score was compared between treatment arms based on a cLDA model with the EORTC-QLQ-C30 GHS/QoL scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9742
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-3.93 to 3.81
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
Hide Description The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who were PD-L1 CPS ≥10.
Time Frame Baseline, Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC-QLQ-C30 assessment, and who were PD-L1 CPS ≥10 were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 184 191
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a Scale
-1.73
(-5.50 to 2.04)
0.04
(-3.77 to 3.85)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments Change from baseline to Week 18 in EORTC-QLQ-C30 GHS/QoL combined score was compared between treatment arms based on a cLDA model with the EORTC-QLQ-C30 GHS/QoL scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4810
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -1.77
Confidence Interval (2-Sided) 95%
-6.71 to 3.17
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants
Hide Description The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores represent a higher ("worse") level of symptoms. Per protocol, change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for all participants in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.
Time Frame Baseline, Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment and completed at least 1 EORTC QLQ-OES18 assessment were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 366 359
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a Scale
Dysphagia subscale
-3.18
(-7.19 to 0.82)
2.36
(-1.77 to 6.49)
Pain subscale
-4.78
(-7.01 to -2.56)
-1.85
(-4.14 to 0.45)
Reflux subscale
-0.22
(-2.81 to 2.36)
0.71
(-1.96 to 3.38)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments DYSPHAGIA: Change from baseline to Week 18 in EORTC QLQ-OES18 Dysphagia subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0436
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -5.54
Confidence Interval (2-Sided) 95%
-10.93 to -0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments PAIN: Change from baseline to Week 18 in EORTC QLQ-OES18 Pain subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0487
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -2.94
Confidence Interval (2-Sided) 95%
-5.86 to -0.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments REFLUX: Change from baseline to Week 18 in EORTC QLQ-OES18 Reflux subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5932
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.93
Confidence Interval (2-Sided) 95%
-4.36 to 2.49
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
Hide Description The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants with ESCC who were PD-L1 CPS≥10 in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.
Time Frame Baseline, Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC QLQ-OES18 assessment, and with ESCC and PD-L1 CPS ≥10 were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 142 135
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a Scale
Dysphagia subscale
-5.11
(-11.51 to 1.30)
3.57
(-3.22 to 10.36)
Pain subscale
-2.55
(-6.11 to 1.01)
-0.42
(-4.20 to 3.36)
Reflux subscale
-0.16
(-4.43 to 4.11)
4.94
(0.43 to 9.46)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments DYSPHAGIA: Change from baseline to Week 18 in EORTC QLQ-OES18 Dysphagia subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0564
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -8.68
Confidence Interval (2-Sided) 95%
-17.59 to 0.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments PAIN: Change from baseline to Week 18 in EORTC QLQ-OES18 Pain subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3813
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -2.13
Confidence Interval (2-Sided) 95%
-6.93 to 2.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments REFLUX: Change from baseline to Week 18 in EORTC QLQ-OES18 Reflux subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0816
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -5.11
Confidence Interval (2-Sided) 95%
-10.86 to 0.65
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC
Hide Description The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants with ESCC in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.
Time Frame Baseline, Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC QLQ-OES18 assessment, and with ESCC were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 270 261
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a Scale
Dysphagia subscale
-1.18
(-5.82 to 3.47)
3.32
(-1.50 to 8.13)
Pain subscale
-4.03
(-6.64 to -1.43)
-2.33
(-5.02 to 0.37)
Reflux subscale
-0.40
(-3.39 to 2.59)
1.09
(-2.01 to 4.19)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments DYSPHAGIA: Change from baseline to Week 18 in EORTC QLQ-OES18 Dysphagia subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1632
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -4.49
Confidence Interval (2-Sided) 95%
-10.81 to 1.83
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments PAIN: Change from baseline to Week 18 in EORTC QLQ-OES18 Pain subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3259
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -1.71
Confidence Interval (2-Sided) 95%
-5.12 to 1.71
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments REFLUX: Change from baseline to Week 18 in EORTC QLQ-OES18 Reflux subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and ECOG performance status (0 versus 1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4598
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -1.50
Confidence Interval (2-Sided) 95%
-5.47 to 2.48
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)
Hide Description The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants who were PD-L1 CPS≥10 in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.
Time Frame Baseline, Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment, completed at least 1 EORTC QLQ-OES18 assessment, and with PD-L1 CPS ≥10 were analyzed.
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Overall Number of Participants Analyzed 184 187
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a Scale
Dysphagia subscale
-7.18
(-12.76 to -1.60)
1.02
(-4.66 to 6.70)
Pain subscale
-3.51
(-6.69 to -0.33)
0.07
(-3.18 to 3.31)
Reflux subscale
-0.52
(-4.17 to 3.14)
4.25
(0.52 to 7.97)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments DYSPHAGIA: Change from baseline to Week 18 in EORTC QLQ-OES18 Dysphagia subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0317
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -8.20
Confidence Interval (2-Sided) 95%
-15.67 to -0.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments PAIN: Change from baseline to Week 18 in EORTC QLQ-OES18 Pain subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0945
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -3.57
Confidence Interval (2-Sided) 95%
-7.77 to 0.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + SOC, Placebo + SOC
Comments REFLUX: Change from baseline to Week 18 in EORTC QLQ-OES18 Reflux subscale was compared between treatment arms based on a cLDA model with EORTC QLQ-OES18 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors including geographic region (Asia versus Rest of the World) and tumor histology (Adenocarcinoma versus Squamous Cell Carcinoma).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0555
Comments [Not Specified]
Method constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -4.76
Confidence Interval (2-Sided) 95%
-9.64 to 0.11
Estimation Comments [Not Specified]
Time Frame Adverse Events: Up to approximately 28 months; All-Cause Mortality: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Adverse Event Reporting Description All-Cause Mortality table includes all randomized participants, Serious and Other AE tables include all treated participants. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug were excluded as AEs.
 
Arm/Group Title Pembrolizumab + SOC Placebo + SOC
Hide Arm/Group Description Participants received pembrolizumab 200 mg IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle. Participants received placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments were administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
All-Cause Mortality
Pembrolizumab + SOC Placebo + SOC
Affected / at Risk (%) Affected / at Risk (%)
Total   262/373 (70.24%)      309/376 (82.18%)    
Hide Serious Adverse Events
Pembrolizumab + SOC Placebo + SOC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   205/370 (55.41%)      204/370 (55.14%)    
Blood and lymphatic system disorders     
Anaemia  1  3/370 (0.81%)  3 10/370 (2.70%)  10
Febrile neutropenia  1  9/370 (2.43%)  9 13/370 (3.51%)  13
Immune thrombocytopenia  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Leukopenia  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Neutropenia  1  5/370 (1.35%)  5 3/370 (0.81%)  3
Pancytopenia  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Thrombocytopenia  1  1/370 (0.27%)  1 3/370 (0.81%)  3
Cardiac disorders     
Acute coronary syndrome  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Acute myocardial infarction  1  2/370 (0.54%)  2 0/370 (0.00%)  0
Angina unstable  1  2/370 (0.54%)  2 0/370 (0.00%)  0
Arteriospasm coronary  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Atrial fibrillation  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Atrial flutter  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Bradycardia  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Cardiac arrest  1  0/370 (0.00%)  0 2/370 (0.54%)  2
Cardiac failure  1  2/370 (0.54%)  2 2/370 (0.54%)  2
Cardio-respiratory arrest  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Coronary artery stenosis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Myocardial infarction  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Palpitations  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Pericardial effusion  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Pericarditis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Supraventricular tachycardia  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Congenital, familial and genetic disorders     
Tracheo-oesophageal fistula  1  3/370 (0.81%)  3 1/370 (0.27%)  1
Endocrine disorders     
Adrenal insufficiency  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Basedow's disease  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Hyperthyroidism  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Hypophysitis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Hypopituitarism  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Inappropriate antidiuretic hormone secretion  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Gastrointestinal disorders     
Abdominal distension  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Abdominal pain  1  0/370 (0.00%)  0 2/370 (0.54%)  2
Abdominal pain upper  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Ascites  1  1/370 (0.27%)  4 0/370 (0.00%)  0
Autoimmune colitis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Colitis  1  4/370 (1.08%)  5 1/370 (0.27%)  1
Constipation  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Diaphragmatic hernia  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Diarrhoea  1  7/370 (1.89%)  7 5/370 (1.35%)  5
Diverticulum intestinal haemorrhagic  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Duodenal perforation  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Duodenitis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Dysphagia  1  17/370 (4.59%)  20 13/370 (3.51%)  13
Enteritis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Enterocolitis  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Enterocutaneous fistula  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Faecaloma  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Gastric fistula  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Gastric haemorrhage  1  3/370 (0.81%)  3 1/370 (0.27%)  1
Gastric ulcer  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Gastrointestinal haemorrhage  1  4/370 (1.08%)  4 4/370 (1.08%)  5
Gastrointestinal obstruction  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Haematemesis  1  1/370 (0.27%)  1 3/370 (0.81%)  3
Haemorrhoids  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Ileus  1  0/370 (0.00%)  0 2/370 (0.54%)  2
Inguinal hernia  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Intestinal obstruction  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Nausea  1  5/370 (1.35%)  5 7/370 (1.89%)  7
Oesophageal fistula  1  2/370 (0.54%)  2 0/370 (0.00%)  0
Oesophageal obstruction  1  5/370 (1.35%)  5 3/370 (0.81%)  3
Oesophageal stenosis  1  1/370 (0.27%)  1 4/370 (1.08%)  4
Pancreatitis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Pneumatosis intestinalis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Stomatitis  1  4/370 (1.08%)  4 5/370 (1.35%)  5
Upper gastrointestinal haemorrhage  1  4/370 (1.08%)  4 6/370 (1.62%)  6
Vomiting  1  9/370 (2.43%)  11 6/370 (1.62%)  7
General disorders     
Asthenia  1  2/370 (0.54%)  2 1/370 (0.27%)  1
Chest discomfort  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Chest pain  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Death  1  2/370 (0.54%)  2 7/370 (1.89%)  7
Fatigue  1  3/370 (0.81%)  3 6/370 (1.62%)  6
General physical health deterioration  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Malaise  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Mucosal inflammation  1  0/370 (0.00%)  0 4/370 (1.08%)  4
Multiple organ dysfunction syndrome  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Pain  1  0/370 (0.00%)  0 1/370 (0.27%)  2
Pneumatosis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Pyrexia  1  5/370 (1.35%)  8 1/370 (0.27%)  1
Strangulated hernia  1  1/370 (0.27%)  2 0/370 (0.00%)  0
Sudden cardiac death  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Systemic inflammatory response syndrome  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Hepatobiliary disorders     
Autoimmune hepatitis  1  2/370 (0.54%)  2 0/370 (0.00%)  0
Bile duct obstruction  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Bile duct stone  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Cholangitis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Cholecystitis chronic  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Granulomatous liver disease  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Hepatic failure  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Hepatic function abnormal  1  2/370 (0.54%)  2 0/370 (0.00%)  0
Hepatitis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Liver disorder  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Immune system disorders     
Hypersensitivity  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Infections and infestations     
Abdominal infection  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Abdominal wall infection  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Abscess  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Acute sinusitis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Anal abscess  1  1/370 (0.27%)  1 1/370 (0.27%)  2
Bacteraemia  1  2/370 (0.54%)  2 2/370 (0.54%)  2
Bronchitis  1  2/370 (0.54%)  2 0/370 (0.00%)  0
COVID-19  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Clostridium difficile colitis  1  1/370 (0.27%)  2 1/370 (0.27%)  1
Cytomegalovirus infection  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Device related infection  1  3/370 (0.81%)  4 0/370 (0.00%)  0
Device related sepsis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Diverticulitis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Extradural abscess  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Gastrointestinal bacterial infection  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Giardiasis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Infection  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Influenza  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Intervertebral discitis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Large intestine infection  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Oral candidiasis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Pneumocystis jirovecii pneumonia  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Pneumonia  1  38/370 (10.27%)  40 32/370 (8.65%)  36
Pneumonia influenzal  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Psoas abscess  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Pulmonary sepsis  1  3/370 (0.81%)  3 0/370 (0.00%)  0
Pulmonary tuberculosis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Pyelonephritis acute  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Respiratory tract infection  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Salmonellosis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Sepsis  1  1/370 (0.27%)  2 5/370 (1.35%)  5
Septic shock  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Skin infection  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Stoma site infection  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Systemic candida  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Upper respiratory tract infection  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Urinary tract infection  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Vascular device infection  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Viral myositis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Injury, poisoning and procedural complications     
Accidental overdose  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Alcohol poisoning  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Anastomotic fistula  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Fall  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Gastrointestinal anastomotic stenosis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Gastrostomy tube site complication  1  0/370 (0.00%)  0 2/370 (0.54%)  2
Hip fracture  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Humerus fracture  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Infusion related reaction  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Post procedural complication  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Product administration error  1  2/370 (0.54%)  2 0/370 (0.00%)  0
Spinal fracture  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Subdural haematoma  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Thoracic vertebral fracture  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Tracheal haemorrhage  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Tracheal obstruction  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Wound dehiscence  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  3/370 (0.81%)  3 2/370 (0.54%)  2
Aspartate aminotransferase increased  1  2/370 (0.54%)  2 2/370 (0.54%)  2
Blood creatinine increased  1  3/370 (0.81%)  3 2/370 (0.54%)  2
Neutrophil count decreased  1  4/370 (1.08%)  4 6/370 (1.62%)  7
Platelet count decreased  1  5/370 (1.35%)  5 10/370 (2.70%)  13
White blood cell count decreased  1  2/370 (0.54%)  2 4/370 (1.08%)  4
Metabolism and nutrition disorders     
Cachexia  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Decreased appetite  1  6/370 (1.62%)  6 6/370 (1.62%)  6
Dehydration  1  6/370 (1.62%)  6 8/370 (2.16%)  9
Hyperammonaemia  1  1/370 (0.27%)  2 0/370 (0.00%)  0
Hypercalcaemia  1  1/370 (0.27%)  1 2/370 (0.54%)  3
Hyperglycaemia  1  2/370 (0.54%)  2 1/370 (0.27%)  1
Hypoalbuminaemia  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Hypocalcaemia  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Hypochloraemia  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Hypoglycaemia  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Hypokalaemia  1  7/370 (1.89%)  7 6/370 (1.62%)  6
Hypomagnesaemia  1  1/370 (0.27%)  1 2/370 (0.54%)  2
Hyponatraemia  1  7/370 (1.89%)  8 6/370 (1.62%)  6
Hypophagia  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Hypovolaemia  1  0/370 (0.00%)  0 1/370 (0.27%)  2
Malnutrition  1  2/370 (0.54%)  4 3/370 (0.81%)  3
Metabolic acidosis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Musculoskeletal and connective tissue disorders     
Arthritis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Back pain  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Bone pain  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Muscle twitching  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Musculoskeletal chest pain  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Osteoporotic fracture  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Polymyalgia rheumatica  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Gastrointestinal submucosal tumour  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Neoplasm swelling  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Tumour associated fever  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Tumour haemorrhage  1  0/370 (0.00%)  0 2/370 (0.54%)  2
Nervous system disorders     
Cerebral haemorrhage  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Cerebral infarction  1  1/370 (0.27%)  1 3/370 (0.81%)  3
Cerebral ischaemia  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Cerebrovascular accident  1  2/370 (0.54%)  2 3/370 (0.81%)  3
Cognitive disorder  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Depressed level of consciousness  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Encephalopathy  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Epilepsy  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Ischaemic stroke  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Loss of consciousness  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Seizure  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Subarachnoid haemorrhage  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Syncope  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Transient ischaemic attack  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Vocal cord paralysis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Product Issues     
Device dislocation  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Device failure  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Device occlusion  1  1/370 (0.27%)  1 2/370 (0.54%)  2
Psychiatric disorders     
Confusional state  1  1/370 (0.27%)  1 3/370 (0.81%)  3
Personality change  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  11/370 (2.97%)  12 6/370 (1.62%)  6
Chronic kidney disease  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Prerenal failure  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Proteinuria  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Renal failure  1  0/370 (0.00%)  0 3/370 (0.81%)  4
Renal impairment  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Renal injury  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Renal tubular necrosis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Tubulointerstitial nephritis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Ureteric obstruction  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Urinary tract obstruction  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Aspiration  1  0/370 (0.00%)  0 2/370 (0.54%)  2
Asthma  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Bronchitis chronic  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Bronchospasm  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Chronic obstructive pulmonary disease  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Dyspnoea  1  2/370 (0.54%)  2 1/370 (0.27%)  1
Emphysema  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Interstitial lung disease  1  2/370 (0.54%)  2 1/370 (0.27%)  1
Oesophagobronchial fistula  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Pleural effusion  1  3/370 (0.81%)  3 1/370 (0.27%)  1
Pleuritic pain  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Pneumonia aspiration  1  11/370 (2.97%)  11 7/370 (1.89%)  8
Pneumonitis  1  12/370 (3.24%)  13 0/370 (0.00%)  0
Pneumothorax  1  1/370 (0.27%)  1 1/370 (0.27%)  1
Pulmonary embolism  1  7/370 (1.89%)  7 7/370 (1.89%)  7
Pulmonary oedema  1  0/370 (0.00%)  0 2/370 (0.54%)  2
Respiratory failure  1  2/370 (0.54%)  2 1/370 (0.27%)  1
Tracheal stenosis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Skin and subcutaneous tissue disorders     
Cold sweat  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Rash maculo-papular  1  2/370 (0.54%)  2 1/370 (0.27%)  1
Subcutaneous emphysema  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Surgical and medical procedures     
Hospitalisation  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Vascular disorders     
Aortic thrombosis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Deep vein thrombosis  1  2/370 (0.54%)  2 3/370 (0.81%)  3
Dry gangrene  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Hypotension  1  2/370 (0.54%)  2 0/370 (0.00%)  0
Jugular vein thrombosis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Orthostatic hypotension  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Peripheral ischaemia  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Subclavian vein thrombosis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Thrombosis  1  1/370 (0.27%)  1 0/370 (0.00%)  0
Vena cava thrombosis  1  0/370 (0.00%)  0 1/370 (0.27%)  1
Venous thrombosis  1  1/370 (0.27%)  1 1/370 (0.27%)  1
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab + SOC Placebo + SOC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   367/370 (99.19%)      364/370 (98.38%)    
Blood and lymphatic system disorders     
Anaemia  1  185/370 (50.00%)  285 200/370 (54.05%)  299
Leukopenia  1  24/370 (6.49%)  54 29/370 (7.84%)  70
Neutropenia  1  94/370 (25.41%)  188 90/370 (24.32%)  177
Thrombocytopenia  1  28/370 (7.57%)  54 37/370 (10.00%)  54
Ear and labyrinth disorders     
Tinnitus  1  36/370 (9.73%)  38 27/370 (7.30%)  30
Endocrine disorders     
Hyperthyroidism  1  19/370 (5.14%)  19 3/370 (0.81%)  4
Hypothyroidism  1  40/370 (10.81%)  46 24/370 (6.49%)  27
Gastrointestinal disorders     
Abdominal pain  1  27/370 (7.30%)  32 18/370 (4.86%)  21
Abdominal pain upper  1  20/370 (5.41%)  21 27/370 (7.30%)  41
Constipation  1  147/370 (39.73%)  237 149/370 (40.27%)  209
Diarrhoea  1  129/370 (34.86%)  226 119/370 (32.16%)  186
Dysphagia  1  46/370 (12.43%)  56 53/370 (14.32%)  66
Nausea  1  245/370 (66.22%)  517 229/370 (61.89%)  503
Stomatitis  1  97/370 (26.22%)  160 92/370 (24.86%)  145
Vomiting  1  121/370 (32.70%)  224 114/370 (30.81%)  199
General disorders     
Asthenia  1  58/370 (15.68%)  103 44/370 (11.89%)  71
Chest pain  1  28/370 (7.57%)  38 20/370 (5.41%)  21
Fatigue  1  147/370 (39.73%)  226 122/370 (32.97%)  181
Malaise  1  47/370 (12.70%)  77 43/370 (11.62%)  64
Mucosal inflammation  1  59/370 (15.95%)  114 65/370 (17.57%)  116
Oedema  1  22/370 (5.95%)  59 20/370 (5.41%)  50
Oedema peripheral  1  16/370 (4.32%)  20 29/370 (7.84%)  34
Pyrexia  1  51/370 (13.78%)  70 43/370 (11.62%)  59
Infections and infestations     
Pneumonia  1  18/370 (4.86%)  19 22/370 (5.95%)  23
Upper respiratory tract infection  1  19/370 (5.14%)  19 15/370 (4.05%)  16
Urinary tract infection  1  12/370 (3.24%)  15 23/370 (6.22%)  27
Investigations     
Alanine aminotransferase increased  1  24/370 (6.49%)  42 25/370 (6.76%)  31
Aspartate aminotransferase increased  1  25/370 (6.76%)  42 27/370 (7.30%)  33
Blood creatinine increased  1  78/370 (21.08%)  128 76/370 (20.54%)  114
Lymphocyte count decreased  1  24/370 (6.49%)  51 21/370 (5.68%)  45
Neutrophil count decreased  1  137/370 (37.03%)  277 107/370 (28.92%)  235
Platelet count decreased  1  59/370 (15.95%)  99 57/370 (15.41%)  96
Weight decreased  1  87/370 (23.51%)  96 90/370 (24.32%)  111
White blood cell count decreased  1  96/370 (25.95%)  215 67/370 (18.11%)  154
Metabolism and nutrition disorders     
Decreased appetite  1  161/370 (43.51%)  279 138/370 (37.30%)  239
Dehydration  1  27/370 (7.30%)  32 25/370 (6.76%)  25
Hyperglycaemia  1  18/370 (4.86%)  25 19/370 (5.14%)  26
Hyperkalaemia  1  26/370 (7.03%)  43 29/370 (7.84%)  42
Hypoalbuminaemia  1  34/370 (9.19%)  43 48/370 (12.97%)  66
Hypocalcaemia  1  27/370 (7.30%)  34 19/370 (5.14%)  25
Hypokalaemia  1  64/370 (17.30%)  106 68/370 (18.38%)  108
Hypomagnesaemia  1  34/370 (9.19%)  43 23/370 (6.22%)  29
Hyponatraemia  1  63/370 (17.03%)  95 71/370 (19.19%)  107
Hypophosphataemia  1  20/370 (5.41%)  27 22/370 (5.95%)  25
Musculoskeletal and connective tissue disorders     
Arthralgia  1  22/370 (5.95%)  26 10/370 (2.70%)  10
Back pain  1  26/370 (7.03%)  32 30/370 (8.11%)  35
Nervous system disorders     
Dizziness  1  35/370 (9.46%)  41 29/370 (7.84%)  37
Dysgeusia  1  38/370 (10.27%)  45 32/370 (8.65%)  35
Headache  1  30/370 (8.11%)  56 25/370 (6.76%)  29
Neuropathy peripheral  1  37/370 (10.00%)  41 37/370 (10.00%)  43
Peripheral sensory neuropathy  1  36/370 (9.73%)  36 30/370 (8.11%)  32
Psychiatric disorders     
Insomnia  1  49/370 (13.24%)  59 44/370 (11.89%)  56
Respiratory, thoracic and mediastinal disorders     
Cough  1  59/370 (15.95%)  69 56/370 (15.14%)  64
Dyspnoea  1  34/370 (9.19%)  39 29/370 (7.84%)  29
Hiccups  1  56/370 (15.14%)  109 53/370 (14.32%)  102
Oropharyngeal pain  1  19/370 (5.14%)  20 12/370 (3.24%)  12
Productive cough  1  22/370 (5.95%)  27 24/370 (6.49%)  24
Skin and subcutaneous tissue disorders     
Alopecia  1  55/370 (14.86%)  55 39/370 (10.54%)  40
Dry skin  1  20/370 (5.41%)  21 9/370 (2.43%)  9
Pruritus  1  31/370 (8.38%)  33 12/370 (3.24%)  13
Rash  1  44/370 (11.89%)  56 26/370 (7.03%)  33
Vascular disorders     
Hypertension  1  24/370 (6.49%)  25 29/370 (7.84%)  35
1
Term from vocabulary, MedDRA 23.0
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 Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03189719    
Other Study ID Numbers: 3475-590
2017-000958-19 ( EudraCT Number )
173739 ( Registry Identifier: JAPIC-CTI )
MK-3475-590 ( Other Identifier: Merck )
KEYNOTE-590 ( Other Identifier: Merck )
First Submitted: June 14, 2017
First Posted: June 16, 2017
Results First Submitted: May 18, 2021
Results First Posted: July 6, 2021
Last Update Posted: January 25, 2022