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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/21/2021.

Study of Pembrolizumab (MK-3475) Versus Investigator's Choice of Chemotherapy for Participants With Advanced Esophageal/Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)-China Extension Study

Clinicaltrials.gov identifier NCT03933449

Recruitment Status Active, not recruiting

First Posted May 1, 2019

Result First Posted February 26, 2020

Last update posted February 26, 2020

Study Description

Brief summary:

In the China extension study, Chinese participants with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the esophagogastric junction (EGJ) that has progressed after first-line standard therapy will be randomized to receive either single agent pembrolizumab or the Investigator's choice of chemotherapy with paclitaxel, docetaxel, or irinotecan. The primary extension study hypothesis is that treatment with pembrolizumab will prolong overall survival (OS) as compared to treatment with chemotherapy.

  • Condition or Disease:Esophageal Carcinoma
    Esophagogastric Junction Carcinoma
  • Intervention/Treatment: Biological: pembrolizumab
    Drug: paclitaxel
    Drug: docetaxel
    Drug: irinotecan
  • Phase: Phase 3
Detailed Description

The China extension study will include participants previously enrolled in China in the global study for MK-3475-181 (NCT02564263) plus those enrolled during the China extension enrollment period.

Study Design
  • Study Type: Interventional
  • Actual Enrollment: 123 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Phase III Randomized Open-Label Study of Single Agent Pembrolizumab vs Physicians' Choice of Single Agent Docetaxel, Paclitaxel, or Irinotecan in Subjects With Advanced/Metastatic Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus That Have Progressed After First-Line Standard Therapy (KEYNOTE-181)
  • Actual Study Start Date: December 2016
  • Estimated Primary Completion Date: February 2019
  • Actual Study Completion Date: December 2021
Arms and interventions
Arm Intervention/treatment
Experimental: Pembrolizumab
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Biological: pembrolizumab
IV infusion
Active Comparator: Chemotherapy
Participants receive Investigator's choice of chemotherapy: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 2 years).
Drug: paclitaxel
IV infusion

Drug: docetaxel
IV infusion

Drug: irinotecan
IV infusion
Outcome Measures
  • Primary Outcome Measures: 1. Overall Survival (OS) in All Participants [ Time Frame: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months) ]
    OS was defined as the time from randomization to death due to any cause. Median OS in all participants is presented.
  • 2. Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) [ Time Frame: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months) ]
    OS was defined as the time from randomization to death due to any cause. Median OS in participants with a PD-L1 CPS ≥10 is presented.
  • 3. Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus [ Time Frame: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months) ]
    OS was defined as the time from randomization to death due to any cause. Median OS in participants with SCC of the esophagus is presented.
  • Secondary Outcome Measures: 1. Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months) ]
    ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of all participants who experienced a CR or PR is presented.
  • 2. Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) [ Time Frame: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months) ]
    ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of participants with a PD-L1 CPS ≥10 who experienced a CR or PR is presented.
  • 3. Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus [ Time Frame: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months) ]
    ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of participants with SCC of the esophagus who experienced a CR or PR is presented.
  • 4. Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months) ]
    PFS was defined as the time from randomization to the first documented progressive disease (PD) 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 must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS as assessed by central imaging vendor review per RECIST 1.1 in all participants is presented.
  • 5. Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) [ Time Frame: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months) ]
    PFS was defined as the time from randomization to the first documented progressive disease (PD) 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 must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS as assessed by central imaging vendor review per RECIST 1.1 is presented for participants with a PD-L1 CPS ≥10.
  • 6. Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus [ Time Frame: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months) ]
    PFS was defined as the time from randomization to the first documented progressive disease (PD) 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 must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS as assessed by central imaging vendor review per RECIST 1.1 is presented for participants with SCC of the esophagus.
  • 7. Number of Participants Experiencing an Adverse Event (AE) [ Time Frame: From first dose of study treatment through end-of-trial analysis data cutoff date of 31-Dec-2021 (Up to approximately 5 years) ]
    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who experienced ≥1 AE will be presented.
  • 8. Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE) [ Time Frame: From first dose of study treatment through to end-of-trial analysis data cutoff date of 31-Dec-2021 (Up to approximately 5 years) ]
    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE will be presented.
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

- Histologically- or cytologically-confirmed diagnosis of adenocarcinoma or squamous
cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ

- Metastatic disease or locally advanced, unresectable disease

- Life expectancy of greater than 3 months

- Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

- Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale

- Documented radiographic or clinical disease progression on no more or less than one
previous line of standard therapy

- Can provide either a newly obtained or archival tumor tissue sample for intra-tumoral
immune-related testing and for anti-programmed cell death (PD)-1

- Participants of reproductive potential must be willing to use adequate contraception
for the course of the study through 120 days after the last dose of pembrolizumab or
through 180 days after the last dose of paclitaxel, docetaxel or irinotecan

- Adequate organ function

Exclusion Criteria:

- Currently participating and receiving study therapy or has participated in a study of
an investigational agent and received study therapy or used an investigational device
within 4 weeks of the first dose of study medication

- Active autoimmune disease that has required systemic treatment in past 2 years

- Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
of immunosuppressive therapy within 7 days prior to the first dose of study medication

- Known central nervous system (CNS) metastases and/or carcinomatous meningitis
(includes past history or current metastasis)

- Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small
molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not
recovered from adverse events due to a previously administered agent

- Has had a severe hypersensitivity reaction to treatment with another mAb

- Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1), or anti-PD-L2 agent, or
previously participated in Merck pembrolizumab (MK-3475) study

- Has a known additional malignancy that has progressed or required active treatment
within the last 5 years with the exception of curatively treated basal cell and
squamous cell carcinoma of the skin and/or curatively resected in-situ cervical and/or
breast cancers, and in-situ or intra-mucosal pharyngeal cancer

- Received a live vaccine within 30 days of the first dose of study medication

- Known history of Human Immunodeficiency Virus (HIV) infection

- Known history of or is positive for hepatitis B (hepatitis B surface antigen reactive)
or known active hepatitis C (hepatitis C virus RNA or hepatitis C antibody is
detected)

- History of non-infectious pneumonitis that required steroids or current pneumonitis

- Active infection requiring systemic therapy

- Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the study

- Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the study starting with the screening visit through 120 days
after the last dose of pembrolizumab or through 180 days after the last dose of
paclitaxel, docetaxel or irinotecan

- Known allergy, hypersensitivity, or contraindication to paclitaxel, docetaxel, or
irinotecan or any components used in their preparation

- Experienced weight loss > 10% over approximately 2 months prior to first dose of study
therapy

- Has ascites or pleural effusion by physical exam

- Has experienced documented objective radiographic or clinical disease progression
during or after receiving more than 1 line of therapy.

Contacts and Locations
Contacts
Locations
Show 23 Study Locations
Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

Study Director: Medical Director Merck Sharp & Dohme Corp.

More Information
  • Responsible Party: Merck Sharp & Dohme Corp.
  • ClinicalTrials.gov Identifier: NCT03933449 History of Changes
  • Other Study ID Numbers: 3475-181 China Extension, 2015-002782-32, 163145, MK-3475-181, KEYNOTE-181
  • First Posted: May 1, 2019 Key Record Dates
  • Last Update Posted: February 26, 2020
  • Last Verified: January 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Yes
  • Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
  • URL: http://engagezone.msd.com/ds_documentation.php
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Merck Sharp & Dohme Corp.: Programmed Cell Death-1 (PD1, PD-1)
    Programmed Death-Ligand 1 (PDL1, PD-L1)
    Programmed Death-Ligand 2 (PDL2, PD-L2)
    Gene expression profiling (GEP)
  • Additional relevant MeSH terms: Carcinoma Esophageal Neoplasms
  • Study Type: Interventional
  • Study Design: Allocation: Randomized;Intervention Model: Parallel Assignment;Masking: None (Open Label);Primary Purpose: Treatment
  • Condition: Esophageal Carcinoma<br/>Esophagogastric Junction Carcinoma
  • Interventions : Biological: pembrolizumab
    Drug: paclitaxel
    Drug: docetaxel
    Drug: irinotecan
  • Enrollment: 123
Participant flow
Recruitment Details This results disclosure is based on a data cutoff date of 13-Feb-2019, at which time 26 participants were ongoing in the study.
Pre-assignment Details
Arm/Group title Chemotherapy Pembrolizumab
Arm/Group Description Participants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle. Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Period Title: Overall Study
Started 61 62
Treated 59 62
Completed 0 0
Not Completed 61 62
Reason Not Completed
Ongoing in Study 6 20
Death 51 36
Adverse Event 4 6
Baseline Characteristics
Arm/Group title TotalChemotherapyPembrolizumab
Arm/Group Description Total of all reporting groupsParticipants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle.Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Overall Number of Baseline Participants 1236162
Baseline Analysis Population Description [Not Specified]
Outcome Measures
1. PrimaryOutcome
Title Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
Description OS was defined as the time from randomization to death due to any cause. Median OS in participants with SCC of the esophagus is presented.
Time Frame From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
The efficacy analysis population consisted of all randomized participants with SCC of the esophagus. Participants were included in the treatment group to which they were randomized.
 
Arm/Group title ChemotherapyPembrolizumab
Arm/Group Description Participants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle.Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Overall Number of Participants Analyzed 5960
Measure Type: Median (95% Confidence Interval)
Unit of Measure: Months
5.6
(4.5 to 7.3)
8.4
(5.8 to 10.9)
Statistical Analysis Overview Comparison Group Selection Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
Comments
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments One-sided p-value based on log-rank test
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.55
Confidence Interval (2-Sided ) 95.0%
0.37 to 0.83
Estimation Comments Based on Cox regression model with treatment as a covariate
2. PrimaryOutcome
Title Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
Description OS was defined as the time from randomization to death due to any cause. Median OS in participants with a PD-L1 CPS ≥10 is presented.
Time Frame From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
The efficacy analysis population consisted of all randomized participants with a PD-L1 CPS ≥10. Participants were included in the treatment group to which they were randomized.
 
Arm/Group title ChemotherapyPembrolizumab
Arm/Group Description Participants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle.Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Overall Number of Participants Analyzed 2925
Measure Type: Median (95% Confidence Interval)
Unit of Measure: Months
5.3
(4.1 to 8.2)
12.0
(6.6 to 0.0)
Statistical Analysis Overview Comparison Group Selection Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
Comments
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments One-sided p-value based on log-rank test
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.34
Confidence Interval (2-Sided ) 95.0%
0.17 to 0.69
Estimation Comments Based on Cox regression model with treatment as a covariate
3. PrimaryOutcome
Title Overall Survival (OS) in All Participants
Description OS was defined as the time from randomization to death due to any cause. Median OS in all participants is presented.
Time Frame From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
The efficacy analysis population consisted of all randomized participants. Participants were included in the treatment group to which they were randomized.
 
Arm/Group title ChemotherapyPembrolizumab
Arm/Group Description Participants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle.Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Overall Number of Participants Analyzed 6162
Measure Type: Median (95% Confidence Interval)
Unit of Measure: Months
5.6
(4.5 to 7.3)
8.4
(5.8 to 10.9)
Statistical Analysis Overview Comparison Group Selection Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Overall Survival (OS) in All Participants
Comments
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments One-sided p-value based on log-rank test
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.55
Confidence Interval (2-Sided ) 95.0%
0.36 to 0.82
Estimation Comments Based on Cox regression model with treatment as a covariate
4. SecondaryOutcome
Title Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE)
Description An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE will be presented.
Time Frame From first dose of study treatment through to end-of-trial analysis data cutoff date of 31-Dec-2021 (Up to approximately 5 years)
Outcome Measure Data
Analysis Population Description
[Not Specified]
 
Arm/Group title
Arm/Group Description
Overall Number of Participants Analyzed
Measure Type:
Unit of Measure:
5. SecondaryOutcome
Title Number of Participants Experiencing an Adverse Event (AE)
Description An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who experienced ≥1 AE will be presented.
Time Frame From first dose of study treatment through end-of-trial analysis data cutoff date of 31-Dec-2021 (Up to approximately 5 years)
Outcome Measure Data
Analysis Population Description
[Not Specified]
 
Arm/Group title
Arm/Group Description
Overall Number of Participants Analyzed
Measure Type:
Unit of Measure:
6. SecondaryOutcome
Title Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
Description PFS was defined as the time from randomization to the first documented progressive disease (PD) 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 must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS as assessed by central imaging vendor review per RECIST 1.1 is presented for participants with SCC of the esophagus.
Time Frame From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
The efficacy analysis population consisted of all randomized participants with SCC of the esophagus. Participants were included in the treatment group to which they were randomized.
 
Arm/Group title ChemotherapyPembrolizumab
Arm/Group Description Participants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle.Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Overall Number of Participants Analyzed 5960
Measure Type: Median (95% Confidence Interval)
Unit of Measure: Months
2.8
(2.0 to 4.2)
2.3
(2.1 to 4.1)
Statistical Analysis Overview Comparison Group Selection Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Overall Survival (OS) in All Participants, Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE), Number of Participants Experiencing an Adverse Event (AE), Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
Comments
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.171
Comments One-sided p-value based on log-rank test
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval (2-Sided ) 95.0%
0.57 to 1.23
Estimation Comments Based on Cox regression model with treatment as a covariate
7. SecondaryOutcome
Title Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
Description PFS was defined as the time from randomization to the first documented progressive disease (PD) 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 must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS as assessed by central imaging vendor review per RECIST 1.1 is presented for participants with a PD-L1 CPS ≥10.
Time Frame From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
The efficacy analysis population consisted of all randomized participants with a PD-L1 CPS ≥10. Participants were included in the treatment group to which they were randomized.
 
Arm/Group title ChemotherapyPembrolizumab
Arm/Group Description Participants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle.Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Overall Number of Participants Analyzed 2925
Measure Type: Median (95% Confidence Interval)
Unit of Measure: Months
4.0
(2.0 to 5.3)
4.0
(2.1 to 6.1)
Statistical Analysis Overview Comparison Group Selection Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Overall Survival (OS) in All Participants, Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE), Number of Participants Experiencing an Adverse Event (AE), Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
Comments
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.238
Comments One-sided p-value based on log-rank test
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided ) 95.0%
0.44 to 1.46
Estimation Comments Based on Cox regression model with treatment as a covariate
8. SecondaryOutcome
Title Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
Description PFS was defined as the time from randomization to the first documented progressive disease (PD) 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 must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS as assessed by central imaging vendor review per RECIST 1.1 in all participants is presented.
Time Frame From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
The efficacy analysis population consisted of all randomized participants. Participants were included in the treatment group to which they were randomized.
 
Arm/Group title ChemotherapyPembrolizumab
Arm/Group Description Participants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle.Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Overall Number of Participants Analyzed 6162
Measure Type: Median (95% Confidence Interval)
Unit of Measure: Months
2.8
(2.0 to 4.2)
2.5
(2.1 to 4.1)
Statistical Analysis Overview Comparison Group Selection Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Overall Survival (OS) in All Participants, Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE), Number of Participants Experiencing an Adverse Event (AE), Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
Comments
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.177
Comments One-sided p-value based on log-rank test
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval (2-Sided ) 95.0%
0.58 to 1.23
Estimation Comments Based on Cox regression model with treatment as a covariate
9. SecondaryOutcome
Title Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
Description ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of participants with SCC of the esophagus who experienced a CR or PR is presented.
Time Frame From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
The efficacy analysis population consisted of all randomized participants with SCC of the esophagus who experienced a confirmed response (CR or PR). Participants were included in the treatment group to which they were randomized.
 
Arm/Group title ChemotherapyPembrolizumab
Arm/Group Description Participants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle.Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Overall Number of Participants Analyzed 5960
Measure Type: Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
3.4
(0.4 to 11.7)
16.7
(8.3 to 28.5)
Statistical Analysis Overview Comparison Group Selection Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Overall Survival (OS) in All Participants, Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE), Number of Participants Experiencing an Adverse Event (AE), Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants, Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
Comments
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0083
Comments One-sided p-value for testing. H0: difference in %=0 versus H1: difference in %>0.
Method Miettinen & Nurminen method
Comments
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 13.3
Confidence Interval (2-Sided ) 95.0%
2.8 to 25.2
Estimation Comments [Not Specified]
10. SecondaryOutcome
Title Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
Description ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of participants with a PD-L1 CPS ≥10 who experienced a CR or PR is presented.
Time Frame From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
The efficacy analysis population consisted of all randomized participants with a PD-L1 CPS ≥10 who experienced a confirmed response (CR or PR). Participants were included in the treatment group to which they were randomized.
 
Arm/Group title ChemotherapyPembrolizumab
Arm/Group Description Participants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle.Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Overall Number of Participants Analyzed 2925
Measure Type: Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
6.9
(0.8 to 22.8)
24.0
(9.4 to 45.1)
Statistical Analysis Overview Comparison Group Selection Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Overall Survival (OS) in All Participants, Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE), Number of Participants Experiencing an Adverse Event (AE), Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants, Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
Comments
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0403
Comments One-sided p-value for testing. H0: difference in %=0 versus H1: difference in %>0.
Method Miettinen & Nurminen method
Comments
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 17.1
Confidence Interval (2-Sided ) 95.0%
-2.3 to 38.0
Estimation Comments [Not Specified]
11. SecondaryOutcome
Title Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
Description ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of all participants who experienced a CR or PR is presented.
Time Frame From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months)
Outcome Measure Data
Analysis Population Description
The efficacy analysis population consisted of all randomized participants who experienced a confirmed response (CR or PR). Participants were included in the treatment group to which they were randomized.
 
Arm/Group title ChemotherapyPembrolizumab
Arm/Group Description Participants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle.Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
Overall Number of Participants Analyzed 6162
Measure Type: Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
3.3
(0.4 to 11.3)
16.1
(8.0 to 27.7)
Statistical Analysis Overview Comparison Group Selection Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Overall Survival (OS) in All Participants, Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE), Number of Participants Experiencing an Adverse Event (AE), Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants, Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus, Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10), Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
Comments
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0084
Comments One-sided p-value for testing. H0: difference in %=0 versus H1: difference in %>0.
Method Miettinen & Nurminen method
Comments
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 12.9
Confidence Interval (2-Sided ) 95.0%
2.7 to 24.5
Estimation Comments [Not Specified]
Adverse Events
Time Frame From first dose of study treatment through analysis data cutoff date of 13-Feb-2019 (Up to approximately 24 months)
Adverse Event Reporting Description Safety: All treated participants; All-Cause Mortality: All randomized participants Per protocol, disease progression of cancer under study was not considered an adverse event (AE) unless considered related to study treatment. Thus, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study treatment are excluded as AEs.
 
Arm/Group Title ChemotherapyPembrolizumab
Arm/Group Description Participants received Investigator’s choice of chemotherapy for up to approximately 2 years: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle.Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 2 years).
All-Cause Mortality
  Pembrolizumab Chemotherapy
Affected at Risk (%) Affected at Risk (%)
Total 42/62 (67.74%) 55/61 (90.16%)
Total
Total, all-cause mortality 42 /62 (67.74%) 55 /61 (90.16%)
Serious Adverse Events
  Pembrolizumab Chemotherapy
Affected / at Risk (%) Events Affected / at Risk (%) Events
Total 22/62 (35.48%) 22/59 (37.29%)
Blood and lymphatic system disorders
Febrile neutropenia 0 /62 (0.00%) 0 1 /59 (1.69%) 1
Bone marrow failure 0 /62 (0.00%) 0 2 /59 (3.39%) 2
Cardiac disorders
Ventricular extrasystoles 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Cardiopulmonary failure 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Gastrointestinal disorders
Vomiting 1 /62 (1.61%) 3 0 /59 (0.00%) 0
Upper gastrointestinal haemorrhage 0 /62 (0.00%) 0 1 /59 (1.69%) 1
Oesophageal obstruction 2 /62 (3.23%) 2 1 /59 (1.69%) 1
Oesophageal fistula 1 /62 (1.61%) 1 2 /59 (3.39%) 2
Gastrointestinal haemorrhage 0 /62 (0.00%) 0 2 /59 (3.39%) 2
Gastrointestinal disorder 0 /62 (0.00%) 0 1 /59 (1.69%) 1
Dysphagia 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Diarrhoea 0 /62 (0.00%) 0 3 /59 (5.08%) 3
Constipation 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Abdominal pain upper 0 /62 (0.00%) 0 1 /59 (1.69%) 1
General disorders
Pyrexia 0 /62 (0.00%) 0 2 /59 (3.39%) 2
Death 2 /62 (3.23%) 2 0 /59 (0.00%) 0
Chest discomfort 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Hepatobiliary disorders
Liver injury 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Autoimmune hepatitis 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Immune system disorders
Anaphylactic reaction 0 /62 (0.00%) 0 1 /59 (1.69%) 1
Infections and infestations
Upper respiratory tract infection 2 /62 (3.23%) 2 1 /59 (1.69%) 1
Respiratory tract infection 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Pneumonia 2 /62 (3.23%) 2 2 /59 (3.39%) 2
Oesophageal infection 0 /62 (0.00%) 0 1 /59 (1.69%) 1
Lymph gland infection 0 /62 (0.00%) 0 1 /59 (1.69%) 1
Lung infection 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Injury, poisoning and procedural complications
Anastomotic fistula 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Investigations
White blood cell count decreased 0 /62 (0.00%) 0 2 /59 (3.39%) 2
Platelet count decreased 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Neutrophil count decreased 0 /62 (0.00%) 0 1 /59 (1.69%) 1
Aspartate aminotransferase increased 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Alanine aminotransferase increased 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Metabolism and nutrition disorders
Malnutrition 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Hyponatraemia 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Hypoglycaemia 0 /62 (0.00%) 0 1 /59 (1.69%) 1
Hypoalbuminaemia 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Hyperglycaemia 0 /62 (0.00%) 0 1 /59 (1.69%) 1
Electrolyte imbalance 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Diabetic ketoacidosis 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Musculoskeletal and connective tissue disorders
Myositis 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Nervous system disorders
Altered state of consciousness 0 /62 (0.00%) 0 1 /59 (1.69%) 1
Psychiatric disorders
Suicide attempt 0 /62 (0.00%) 0 2 /59 (3.39%) 2
Renal and urinary disorders
Urinary retention 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Acute kidney injury 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Respiratory, thoracic and mediastinal disorders
Pneumonitis 1 /62 (1.61%) 1 0 /59 (0.00%) 0
Haemoptysis 0 /62 (0.00%) 0 2 /59 (3.39%) 2
Acquired tracheo-oesophageal fistula 1 /62 (1.61%) 1 1 /59 (1.69%) 1
Total
Total, serious adverse events 22 /62 (35.48%) 0 22 /59 (37.29%) 0
Show Other (Not Including Serious) Adverse Events
  Pembrolizumab Chemotherapy
Affected / at Risk (%) Events Affected / at Risk (%) Events
Total 57/62 (91.94%) 55/59 (93.22%)
Blood and lymphatic system disorders
Neutropenia 0 /62 (0.00%) 0 5 /59 (8.47%) 17
Leukopenia 1 /62 (1.61%) 2 7 /59 (11.86%) 23
Anaemia 15 /62 (24.19%) 20 30 /59 (50.85%) 47
Endocrine disorders
Hypothyroidism 12 /62 (19.35%) 15 2 /59 (3.39%) 2
Gastrointestinal disorders
Vomiting 5 /62 (8.06%) 8 19 /59 (32.20%) 36
Nausea 6 /62 (9.68%) 6 16 /59 (27.12%) 22
Gastrooesophageal reflux disease 6 /62 (9.68%) 8 6 /59 (10.17%) 7
Dysphagia 4 /62 (6.45%) 4 3 /59 (5.08%) 3
Diarrhoea 7 /62 (11.29%) 8 17 /59 (28.81%) 39
Constipation 10 /62 (16.13%) 13 10 /59 (16.95%) 14
Abdominal pain upper 5 /62 (8.06%) 7 4 /59 (6.78%) 4
Abdominal pain 3 /62 (4.84%) 5 3 /59 (5.08%) 3
Abdominal distension 4 /62 (6.45%) 4 1 /59 (1.69%) 1
General disorders
Pyrexia 4 /62 (6.45%) 6 9 /59 (15.25%) 13
Malaise 2 /62 (3.23%) 2 6 /59 (10.17%) 7
Fatigue 3 /62 (4.84%) 5 10 /59 (16.95%) 10
Chest pain 5 /62 (8.06%) 6 1 /59 (1.69%) 1
Asthenia 12 /62 (19.35%) 12 4 /59 (6.78%) 4
Hepatobiliary disorders
Hepatic function abnormal 4 /62 (6.45%) 4 2 /59 (3.39%) 2
Infections and infestations
Upper respiratory tract infection 4 /62 (6.45%) 4 2 /59 (3.39%) 2
Pneumonia 5 /62 (8.06%) 5 3 /59 (5.08%) 3
Lung infection 4 /62 (6.45%) 6 5 /59 (8.47%) 5
Investigations
White blood cell count increased 2 /62 (3.23%) 2 3 /59 (5.08%) 3
White blood cell count decreased 4 /62 (6.45%) 7 28 /59 (47.46%) 79
Weight decreased 12 /62 (19.35%) 12 16 /59 (27.12%) 18
Tri-iodothyronine decreased 1 /62 (1.61%) 1 3 /59 (5.08%) 3
Platelet count decreased 3 /62 (4.84%) 3 5 /59 (8.47%) 6
Neutrophil count increased 1 /62 (1.61%) 1 3 /59 (5.08%) 3
Neutrophil count decreased 2 /62 (3.23%) 3 17 /59 (28.81%) 54
Lymphocyte count decreased 1 /62 (1.61%) 1 8 /59 (13.56%) 10
Haemoglobin decreased 0 /62 (0.00%) 0 3 /59 (5.08%) 3
Gamma-glutamyltransferase increased 7 /62 (11.29%) 7 4 /59 (6.78%) 4
Blood urea increased 2 /62 (3.23%) 3 3 /59 (5.08%) 4
Blood lactate dehydrogenase increased 2 /62 (3.23%) 2 4 /59 (6.78%) 4
Blood glucose increased 1 /62 (1.61%) 1 3 /59 (5.08%) 3
Blood chloride decreased 0 /62 (0.00%) 0 3 /59 (5.08%) 4
Blood bilirubin increased 4 /62 (6.45%) 4 2 /59 (3.39%) 3
Aspartate aminotransferase increased 5 /62 (8.06%) 6 5 /59 (8.47%) 8
Alanine aminotransferase increased 11 /62 (17.74%) 12 4 /59 (6.78%) 6
Metabolism and nutrition disorders
Hypoproteinaemia 3 /62 (4.84%) 3 4 /59 (6.78%) 6
Hypophosphataemia 2 /62 (3.23%) 2 3 /59 (5.08%) 4
Hyponatraemia 3 /62 (4.84%) 3 4 /59 (6.78%) 6
Hypokalaemia 5 /62 (8.06%) 5 11 /59 (18.64%) 14
Hypochloraemia 4 /62 (6.45%) 6 1 /59 (1.69%) 1
Hypoalbuminaemia 13 /62 (20.97%) 19 11 /59 (18.64%) 12
Hyperglycaemia 5 /62 (8.06%) 5 3 /59 (5.08%) 4
Hypercalcaemia 4 /62 (6.45%) 4 1 /59 (1.69%) 1
Decreased appetite 11 /62 (17.74%) 12 11 /59 (18.64%) 13
Musculoskeletal and connective tissue disorders
Back pain 7 /62 (11.29%) 7 1 /59 (1.69%) 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain 5 /62 (8.06%) 5 3 /59 (5.08%) 3
Psychiatric disorders
Insomnia 3 /62 (4.84%) 3 4 /59 (6.78%) 4
Renal and urinary disorders
Proteinuria 6 /62 (9.68%) 6 1 /59 (1.69%) 2
Haematuria 2 /62 (3.23%) 3 3 /59 (5.08%) 3
Respiratory, thoracic and mediastinal disorders
Productive cough 3 /62 (4.84%) 3 7 /59 (11.86%) 7
Hiccups 0 /62 (0.00%) 0 3 /59 (5.08%) 3
Dyspnoea 6 /62 (9.68%) 8 1 /59 (1.69%) 1
Dysphonia 2 /62 (3.23%) 2 3 /59 (5.08%) 3
Cough 11 /62 (17.74%) 17 7 /59 (11.86%) 9
Skin and subcutaneous tissue disorders
Rash 4 /62 (6.45%) 5 1 /59 (1.69%) 1
Alopecia 0 /62 (0.00%) 0 7 /59 (11.86%) 7
Total
Total, other adverse events 57 /62 (91.94%) 0 55 /59 (93.22%) 0
Limitations and Caveats

[Not Specified]

More Information
Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 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
  • ClinicalTrials.gov Identifier: NCT03933449 History of Changes
  • Other Study ID Numbers: KEYNOTE-181
  • First Submitted: April 29, 2019
  • First Posted: May 1, 2019
  • Results First Submitted: February 12, 2020
  • Results First Posted: February 26, 2020
  • Last Update Posted: February 26, 2020