Esophageal Carcinoma, Esophagogastric Junction Carcinoma
Conditions
Keywords
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)
Brief summary
In this study, participants with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the esophagogastric junction (EGJ) that had progressed after first-line standard therapy were randomized to receive either pembrolizumab (MK-3475) OR the Investigator's choice of standard chemotherapy with paclitaxel, docetaxel, or irinotecan. The primary study hypothesis was that treatment with pembrolizumab would prolong overall survival (OS) as compared to treatment with standard chemotherapy.
Interventions
BIOLOGICALpembrolizumab
200 mg administered as IV infusion on Day 1 of every 21-day cycle
DRUGpaclitaxel
80-100 mg/m\^2 administered as IV infusion on Days 1, 8, and 15 of each 28-day cycle
DRUGdocetaxel
75 mg/m\^2 administered as IV infusion on Day 1 of every 21-day cycle
DRUGirinotecan
180 mg/m\^2 administered as IV infusion on Day 1 of every 14-day cycle
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 treatment * 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 treatment * 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 treatment * Known history of human immunodeficiency virus (HIV) infection * Known history of or is positive for hepatitis B or known active hepatitis C * 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 treatment * Has ascites or pleural effusion by physical exam * Has experienced documented objective radiographic or clinical disease progression during or after receiving \>1 line of therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus | Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 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. |
| Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) | Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 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. |
| Overall Survival (OS) in All Participants | Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months) | OS was defined as the time from randomization to death due to any cause. Median OS in all participants is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 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 blinded independent central review per RECIST 1.1 is presented for participants with a PD-L1 CPS ≥10. |
| 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 | Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 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. The percentage of participants with SCC of the esophagus who experienced a CR or PR is presented. |
| Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 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 blinded independent central review per RECIST 1.1 in all participants is presented. |
| Number of Participants Experiencing an Adverse Event (AE) | Through End-of-Trial Analysis data cutoff date of 14-Mar-2022 (up to approximately 6 years) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 who experienced ≥1 AE is presented. |
| Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE) | Through End-of-Trial Analysis data cutoff date of 14-Mar-2022 (up to approximately 6 years) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 who discontinued study treatment due to an AE is presented. |
| 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) | Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 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. The percentage of participants with a PD-L1 CPS ≥10 who experienced a CR or PR is presented. |
| Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 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. The percentage of all participants who experienced a CR or PR is presented. |
| 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 | Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 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 blinded independent central review per RECIST 1.1 is presented for participants with SCC of the esophagus. |
Participant flow
Pre-assignment details
At the time of the primary analysis data cut-off of 15-Oct-2018, 67 participants were ongoing in the study.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months). | 314 |
| Chemotherapy Participants received Investigator's choice of 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 19 months). | 314 |
| Total | 628 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 31 | 29 |
| Overall Study | Death | 270 | 262 |
| Overall Study | Sponsor's decision | 9 | 4 |
| Overall Study | Withdrawal by Subject | 4 | 19 |
Baseline characteristics
| Characteristic | Pembrolizumab | Chemotherapy | Total |
|---|---|---|---|
| Age, Continuous | 62.6 Years STANDARD_DEVIATION 9.4 | 62.0 Years STANDARD_DEVIATION 9.6 | 62.3 Years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 25 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 288 Participants | 273 Participants | 561 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 16 Participants | 23 Participants |
| Geographic Region Asia | 121 Participants | 122 Participants | 243 Participants |
| Geographic Region RoW | 193 Participants | 192 Participants | 385 Participants |
| Programmed Death-Ligand 1 (PD-L1) Status: Combined Positive Score (CPS) Not Evaluable | 6 Participants | 3 Participants | 9 Participants |
| Programmed Death-Ligand 1 (PD-L1) Status: Combined Positive Score (CPS) PD-L1 CPS <10 | 199 Participants | 194 Participants | 393 Participants |
| Programmed Death-Ligand 1 (PD-L1) Status: Combined Positive Score (CPS) PD-L1 CPS ≥10 | 109 Participants | 117 Participants | 226 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 126 Participants | 122 Participants | 248 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 11 Participants | 15 Participants |
| Race (NIH/OMB) White | 179 Participants | 172 Participants | 351 Participants |
| Sex: Female, Male Female | 41 Participants | 43 Participants | 84 Participants |
| Sex: Female, Male Male | 273 Participants | 271 Participants | 544 Participants |
| Tumor Histology Adenocarcinoma of esophagus & EGJ Siewert type I | 115 Participants | 110 Participants | 225 Participants |
| Tumor Histology Squamous cell carcinoma | 199 Participants | 204 Participants | 403 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 305 / 314 | 305 / 314 | 3 / 5 |
| other Total, other adverse events | 285 / 314 | 281 / 296 | 5 / 5 |
| serious Total, serious adverse events | 127 / 314 | 121 / 296 | 1 / 5 |
Outcome results
Primary
Overall Survival (OS) in All Participants
OS was defined as the time from randomization to death due to any cause. Median OS in all participants is presented.
Time frame: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
Population: The efficacy analysis population consisted of all randomized participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival (OS) in All Participants | 7.1 Months |
| Chemotherapy | Overall Survival (OS) in All Participants | 7.1 Months |
p-value: 0.053195% CI: [0.75, 1.05]Log Rank
Primary
Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
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: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) | 9.3 Months |
| Chemotherapy | Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) | 6.7 Months |
p-value: 0.0085595% CI: [0.52, 0.94]Log Rank
Primary
Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
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: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus | 8.2 Months |
| Chemotherapy | Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus | 7.1 Months |
p-value: 0.0089495% CI: [0.63, 0.96]Log Rank
Secondary
Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 who discontinued study treatment due to an AE is presented.
Time frame: Through End-of-Trial Analysis data cutoff date of 14-Mar-2022 (up to approximately 6 years)
Population: The analysis population consisted of all randomized participants who received at least 1 dose of study treatment. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE) | 40 Participants |
| Chemotherapy | Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE) | 42 Participants |
Secondary
Number of Participants Experiencing an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 who experienced ≥1 AE is presented.
Time frame: Through End-of-Trial Analysis data cutoff date of 14-Mar-2022 (up to approximately 6 years)
Population: The analysis population consisted of all randomized participants who received at least 1 dose of study treatment. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants Experiencing an Adverse Event (AE) | 301 Participants |
| Chemotherapy | Number of Participants Experiencing an Adverse Event (AE) | 288 Participants |
Secondary
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
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. The percentage of all participants who experienced a CR or PR is presented.
Time frame: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
Population: The efficacy analysis population consisted of all randomized participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 13.1 Percentage of Participants |
| Chemotherapy | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 6.7 Percentage of Participants |
p-value: 0.003795% CI: [1.7, 11.2]Miettinen & Nurminen method
Secondary
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)
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. The percentage of participants with a PD-L1 CPS ≥10 who experienced a CR or PR is presented.
Time frame: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | 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) | 21.5 Percentage of Participants |
| Chemotherapy | 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) | 6.1 Percentage of Participants |
p-value: 0.000695% CI: [6.2, 24.7]Miettinen & Nurminen method
Secondary
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
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. The percentage of participants with SCC of the esophagus who experienced a CR or PR is presented.
Time frame: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | 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 | 16.7 Percentage of Participants |
| Chemotherapy | 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 | 7.4 Percentage of Participants |
p-value: 0.002295% CI: [3, 15.8]Miettinen & Nurminen method
Secondary
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
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 blinded independent central review per RECIST 1.1 in all participants is presented.
Time frame: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
Population: The efficacy analysis population consisted of all randomized participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 2.1 Months |
| Chemotherapy | Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 3.4 Months |
p-value: 0.28795% CI: [0.94, 1.31]Log Rank
Secondary
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)
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 blinded independent central review per RECIST 1.1 is presented for participants with a PD-L1 CPS ≥10.
Time frame: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | 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) | 2.6 Months |
| Chemotherapy | 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) | 3.0 Months |
p-value: 0.01595% CI: [0.54, 0.97]Log Rank
Secondary
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
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 blinded independent central review per RECIST 1.1 is presented for participants with SCC of the esophagus.
Time frame: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | 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 | 2.2 Months |
| Chemotherapy | 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 | 3.1 Months |
p-value: 0.21695% CI: [0.75, 1.13]Log Rank