Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/KEYNOTE-042)
Study Details
Study Description
Brief Summary
In this study, participants with programmed cell death ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) will be randomized to receive single agent pembrolizumab for up to 35 treatments or standard of care (SOC) platinum-based chemotherapy (carboplatin + paclitaxel or carboplatin + pemetrexed for 4 to 6 21-day cycles). Participants in the platinum-based chemotherapy arms with non-squamous tumor histologies may receive pemetrexed maintenance therapy after the 4 to 6 cycles of chemotherapy. The primary study hypothesis is that pembrolizumab prolongs overall survival (OS) compared to SOC chemotherapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The global study for MK-3475-042 enrolled 1274 participants. Of the 1274 total participants enrolled in the global study, 92 were also enrolled in the China extension study for MK-3475-042 (NCT03850444).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pembrolizumab Participants receive pembrolizumab 200 mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments. |
Biological: pembrolizumab
Other Names:
|
| Active Comparator: SOC Treatment Participants receive carboplatin target dose Area Under Curve (AUC) 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 IV on Day 1 of every 21-day cycle (Q3W) for a maximum of 6 cycles OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 IV on Day 1 Q3W for a maximum of 6 cycles; participants with non-squamous histologies may go on to receive optional treatment with pemetrexed 500 mg/m^2 IV on Day 1 Q3W. |
Drug: carboplatin
Other Names:
Drug: paclitaxel
Other Names:
Drug: pemetrexed
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50% [Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)]
OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented.
- Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20% [Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)]
OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented.
- Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1% [Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)]
OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented.
Secondary Outcome Measures
- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50% [Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)]
PFS was determined for participants with a TPS of ≥50% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥50% is presented.
- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20% [Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)]
PFS was determined for participants with a TPS of ≥20% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥20% is presented.
- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1% [Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)]
PFS was determined for participants with a TPS of ≥1% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥1% is presented.
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50% [Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)]
ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and 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, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented.
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20% [Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)]
ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and 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, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented.
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1% [Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)]
ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and 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, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented.
- Number of Participants Who Experienced At Least One Adverse Event (AE) [Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)]
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. An AE can therefore be any unfavorable 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 study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. These safety results are based on a 26-February-2018 data cutoff date.
- Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)]
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. An AE can therefore be any unfavorable 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 study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. These safety results are based on a 26-February-2018 data cutoff date.
Eligibility Criteria
Criteria
Inclusion criteria:
-
Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC
-
PD-L1 positive tumor
-
Measureable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
-
Life expectancy of at least 3 months
-
No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease)
-
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
-
Adequate organ function
-
No prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
-
Submission of formalin-fixed diagnostic tumor tissue (in the case of participants having received adjuvant systemic therapy, the tissue should be taken after completion of this therapy)
-
Female participants of childbearing potential must have a negative urine or serum pregnancy test and must be willing to use two adequate barrier methods of contraception or a barrier method plus a hormonal method starting with the screening visit through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study
-
Male participants with a female partner(s) of child-bearing potential must be willing to use two adequate barrier methods of contraception from screening through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study
Exclusion criteria:
-
Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or is echinoderm microtubule-associated protein-like 4(EML4) gene/anaplastic lymphoma kinase (ALK) gene fusion positive
-
Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy
-
No tumor specimen evaluable for PD-L1 expression by the central study laboratory
-
Squamous histology and received carboplatin in combination with paclitaxel in the adjuvant setting
-
Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication with the exception of daily steroid replacement therapy
-
The NSCLC can be treated with curative intent with either surgical resection and/or chemoradiation
-
Expected to require any other form of systemic or localized antineoplastic therapy while on study
-
Any prior systemic cytotoxic chemotherapy, biological therapy or major surgery within 3 weeks of the first dose of study therapy; received lung radiation therapy >30 Gy within 6 months of the first dose of study therapy
-
Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
-
Known central nervous system metastases and/or carcinomatous meningitis
-
Active autoimmune disease that has required systemic treatment in the past 2 years
-
Had allogeneic tissue/solid organ transplantation
-
Interstitial lung disease or history of pneumonitis that has required oral or IV steroids
-
Has received or will receive a live vaccine within 30 days prior to the first study therapy (seasonal flu vaccines that do not contain live vaccine are permitted)
-
Active infection requiring intravenous systemic therapy
-
Known history of human immunodeficiency virus (HIV)
-
Known active Hepatitis B or C
-
Regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
-
Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 3475-042
- 152877
- MK-3475-042
- KEYNOTE-042
- 2014-001473-14
Study Results
Participant Flow
| Recruitment Details | Of the 1275 participants randomized (pembrolizumab=638, chemotherapy=637), 1 participant assigned to receive pembrolizumab died prior to randomization and was randomized in error. The intent to treat population was defined as participants alive at the time of randomization, so the actual randomized population included 637 participants in each arm. |
|---|---|
| Pre-assignment Detail | These interim results are based on a database cutoff date of 26-February-2018, at which time 448 participants were ongoing in the study. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (Standard of Care [SOC] Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 every 3 weeks (Q3W) for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose Area Under Curve (AUC) 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Period Title: Overall Study | ||
| STARTED | 637 | 637 |
| Treated | 636 | 615 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 637 | 637 |
Baseline Characteristics
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) | Total |
|---|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W | Total of all reporting groups |
| Overall Participants | 637 | 637 | 1274 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
62.5
(9.9)
|
63.1
(9.4)
|
62.8
(9.7)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
187
29.4%
|
185
29%
|
372
29.2%
|
| Male |
450
70.6%
|
452
71%
|
902
70.8%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
10
1.6%
|
5
0.8%
|
15
1.2%
|
| Asian |
189
29.7%
|
187
29.4%
|
376
29.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
0.2%
|
1
0.1%
|
| Black or African American |
10
1.6%
|
13
2%
|
23
1.8%
|
| White |
398
62.5%
|
412
64.7%
|
810
63.6%
|
| More than one race |
30
4.7%
|
19
3%
|
49
3.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Count of Participants) | |||
| ECOG PS=0 |
198
31.1%
|
192
30.1%
|
390
30.6%
|
| ECOG PS=1 |
439
68.9%
|
445
69.9%
|
884
69.4%
|
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status (Count of Participants) | |||
| TPS=≥50% |
299
46.9%
|
300
47.1%
|
599
47%
|
| TPS=20-49% |
114
17.9%
|
105
16.5%
|
219
17.2%
|
| TPS=1-19% |
224
35.2%
|
232
36.4%
|
456
35.8%
|
| TPS=<1% |
0
0%
|
0
0%
|
0
0%
|
| Tumor Histology (Count of Participants) | |||
| Squamous |
243
38.1%
|
249
39.1%
|
492
38.6%
|
| Non-squamous |
394
61.9%
|
388
60.9%
|
782
61.4%
|
Outcome Measures
| Title | Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50% |
|---|---|
| Description | OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented. |
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Measure Participants | 299 | 300 |
| Median (95% Confidence Interval) [Months] |
20.0
|
12.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Chemotherapy (SOC Treatment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | One-sided p-value based on stratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.69 | |
| Confidence Interval |
(2-Sided) 95% 0.56 to 0.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), and histology (squamous vs. non-squamous). | |
| Title | Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20% |
|---|---|
| Description | OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented. |
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Measure Participants | 413 | 405 |
| Median (95% Confidence Interval) [Months] |
17.7
|
13.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Chemotherapy (SOC Treatment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0020 |
| Comments | One-sided p-value based on stratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.77 | |
| Confidence Interval |
(2-Sided) 95% 0.64 to 0.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous). | |
| Title | Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1% |
|---|---|
| Description | OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented. |
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Measure Participants | 637 | 637 |
| Median (95% Confidence Interval) [Months] |
16.7
|
12.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Chemotherapy (SOC Treatment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0018 |
| Comments | One-sided p-value based on stratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.81 | |
| Confidence Interval |
(2-Sided) 95% 0.71 to 0.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous). | |
| Title | Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50% |
|---|---|
| Description | PFS was determined for participants with a TPS of ≥50% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥50% is presented. |
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Measure Participants | 299 | 300 |
| Median (95% Confidence Interval) [Months] |
6.9
|
6.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Chemotherapy (SOC Treatment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0187 |
| Comments | One-sided p-value based on stratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.82 | |
| Confidence Interval |
(2-Sided) 95% 0.68 to 0.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1) and histology (squamous vs. non-squamous). | |
| Title | Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20% |
|---|---|
| Description | PFS was determined for participants with a TPS of ≥20% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥20% is presented. |
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Measure Participants | 413 | 405 |
| Median (95% Confidence Interval) [Months] |
6.2
|
6.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Chemotherapy (SOC Treatment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2331 |
| Comments | One-sided p-value based on stratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.94 | |
| Confidence Interval |
(2-Sided) 95% 0.80 to 1.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous). | |
| Title | Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1% |
|---|---|
| Description | PFS was determined for participants with a TPS of ≥1% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥1% is presented. |
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Measure Participants | 637 | 637 |
| Median (95% Confidence Interval) [Months] |
5.4
|
6.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Chemotherapy (SOC Treatment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8445 |
| Comments | One-sided p-value based on stratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.07 | |
| Confidence Interval |
(2-Sided) 95% 0.94 to 1.21 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous). | |
| Title | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50% |
|---|---|
| Description | ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and 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, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented. |
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Measure Participants | 299 | 300 |
| Number (95% Confidence Interval) [Percentage of participants] |
39.5
6.2%
|
32.0
5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Chemotherapy (SOC Treatment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0289 |
| Comments | One-sided p-value for testing. H0: difference in percentages=0 vs. H1: difference in percentages >0 | |
| Method | Stratified Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage (DP) |
| Estimated Value | 7.4 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 15.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | DP for pembrolizumab vs. chemotherapy based on Miettinen & Nurminen method stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1) and histology (squamous vs. nonsquamous). | |
| Title | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20% |
|---|---|
| Description | ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and 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, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented. |
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Measure Participants | 413 | 405 |
| Number (95% Confidence Interval) [Percentage of participants] |
33.4
5.2%
|
28.9
4.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Chemotherapy (SOC Treatment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0638 |
| Comments | One-sided p-value for testing. H0: difference in percentages=0 vs. H1: difference in percentages >0 | |
| Method | Stratified Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage (DP) |
| Estimated Value | 4.9 | |
| Confidence Interval |
(2-Sided) 95% -1.4 to 11.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | DP for pembrolizumab vs. chemotherapy based on Miettinen & Nurminen method stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous). | |
| Title | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1% |
|---|---|
| Description | ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and 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, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented. |
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Measure Participants | 637 | 637 |
| Number (95% Confidence Interval) [Percentage of participants] |
27.3
4.3%
|
26.5
4.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Chemotherapy (SOC Treatment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3798 |
| Comments | One-sided p-value for testing. H0: difference in percentages=0 vs. H1: difference in percentages >0 | |
| Method | Stratified Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage (DP) |
| Estimated Value | 0.7 | |
| Confidence Interval |
(2-Sided) 95% -4.0 to 5.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | DP for pembrolizumab vs. chemotherapy based on Miettinen & Nurminen method stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous). | |
| Title | Number of Participants Who Experienced At Least One 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. An AE can therefore be any unfavorable 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 study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. These safety results are based on a 26-February-2018 data cutoff date. |
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all participants who received ≥1 dose of study treatment. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Measure Participants | 636 | 615 |
| Count of Participants [Participants] |
610
95.8%
|
606
95.1%
|
| Title | Number of Participants Who Discontinued Study Treatment Due to 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. An AE can therefore be any unfavorable 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 study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. These safety results are based on a 26-February-2018 data cutoff date. |
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all participants who received ≥1 dose of study treatment. |
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W |
| Measure Participants | 636 | 615 |
| Count of Participants [Participants] |
122
19.2%
|
89
14%
|
Adverse Events
| Time Frame | Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Population: All participants receiving ≥1 dose of study treatment. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study drug are excluded as AEs. | |||
| Arm/Group Title | Pembrolizumab | Chemotherapy (SOC Treatment) | ||
| Arm/Group Description | Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W | ||
All Cause Mortality |
||||
| Pembrolizumab | Chemotherapy (SOC Treatment) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 370/636 (58.2%) | 427/615 (69.4%) | ||
Serious Adverse Events |
||||
| Pembrolizumab | Chemotherapy (SOC Treatment) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 259/636 (40.7%) | 187/615 (30.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/636 (0.5%) | 3 | 17/615 (2.8%) | 24 |
| Febrile neutropenia | 1/636 (0.2%) | 1 | 15/615 (2.4%) | 15 |
| Leukopenia | 0/636 (0%) | 0 | 2/615 (0.3%) | 2 |
| Lymphadenopathy | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Neutropenia | 0/636 (0%) | 0 | 6/615 (1%) | 6 |
| Normochromic anaemia | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Splenic infarction | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Thrombocytopenia | 1/636 (0.2%) | 1 | 4/615 (0.7%) | 4 |
| Agranulocytosis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Bone marrow failure | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Pancytopenia | 0/636 (0%) | 0 | 3/615 (0.5%) | 3 |
| Cardiac disorders | ||||
| Acute coronary syndrome | 0/636 (0%) | 0 | 3/615 (0.5%) | 3 |
| Acute myocardial infarction | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Aortic valve stenosis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Arrhythmia | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Atrial fibrillation | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Atrial flutter | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Cardiac arrest | 3/636 (0.5%) | 3 | 0/615 (0%) | 0 |
| Cardiac failure | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Cardiac failure acute | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Cardiac tamponade | 3/636 (0.5%) | 3 | 0/615 (0%) | 0 |
| Cardio-respiratory arrest | 2/636 (0.3%) | 2 | 1/615 (0.2%) | 1 |
| Cardiopulmonary failure | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Myocardial infarction | 3/636 (0.5%) | 3 | 0/615 (0%) | 0 |
| Myocarditis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Pericardial effusion | 6/636 (0.9%) | 6 | 0/615 (0%) | 0 |
| Pericarditis | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Sinus tachycardia | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Supraventricular tachycardia | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Ventricular fibrillation | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Vertigo | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Endocrine disorders | ||||
| Adrenal insufficiency | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Hyperthyroidism | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Hypophysitis | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Hypopituitarism | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Hypothyroidism | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Hypercalcaemia of malignancy | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Colitis | 5/636 (0.8%) | 5 | 0/615 (0%) | 0 |
| Constipation | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Diarrhoea | 4/636 (0.6%) | 4 | 2/615 (0.3%) | 2 |
| Duodenal perforation | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Dyspepsia | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Enterocolitis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Gastric haemorrhage | 1/636 (0.2%) | 2 | 0/615 (0%) | 0 |
| Gastric ulcer haemorrhage | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Gastritis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Gastrointestinal haemorrhage | 1/636 (0.2%) | 2 | 1/615 (0.2%) | 1 |
| Gastrointestinal ulcer | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Glossitis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Ileus | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Incarcerated inguinal hernia | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Inguinal hernia | 0/636 (0%) | 0 | 2/615 (0.3%) | 2 |
| Intestinal ischaemia | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Melaena | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Nausea | 3/636 (0.5%) | 3 | 2/615 (0.3%) | 2 |
| Neutropenic colitis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Oesophageal fistula | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Pancreatic mass | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Rectal ulcer | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Stomatitis | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 0/636 (0%) | 0 | 1/615 (0.2%) | 2 |
| Volvulus | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Vomiting | 2/636 (0.3%) | 2 | 2/615 (0.3%) | 2 |
| General disorders | ||||
| Accidental death | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Asthenia | 1/636 (0.2%) | 1 | 4/615 (0.7%) | 4 |
| Death | 10/636 (1.6%) | 10 | 5/615 (0.8%) | 5 |
| Fatigue | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| General physical health deterioration | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Ill-defined disorder | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Malaise | 1/636 (0.2%) | 1 | 2/615 (0.3%) | 2 |
| Performance status decreased | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Pyrexia | 4/636 (0.6%) | 4 | 1/615 (0.2%) | 1 |
| Sudden death | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Sudden cardiac death | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Hepatobiliary disorders | ||||
| Autoimmune hepatitis | 4/636 (0.6%) | 4 | 0/615 (0%) | 0 |
| Hepatic function abnormal | 2/636 (0.3%) | 2 | 1/615 (0.2%) | 1 |
| Hepatitis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Hepatitis acute | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Hepatitis toxic | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Immune system disorders | ||||
| Anaphylactic reaction | 1/636 (0.2%) | 1 | 2/615 (0.3%) | 2 |
| Contrast media allergy | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Infections and infestations | ||||
| Abdominal sepsis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Amoebiasis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Amoebic dysentery | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Anal abscess | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Biliary sepsis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Bronchitis | 7/636 (1.1%) | 7 | 2/615 (0.3%) | 2 |
| Candida infection | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Cellulitis | 1/636 (0.2%) | 1 | 2/615 (0.3%) | 3 |
| Clostridium difficile infection | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Cystitis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Device related infection | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Diverticulitis | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Enterocolitis infectious | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Gastroenteritis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Gastroenteritis viral | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Herpes zoster | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Infection | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Infectious pleural effusion | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Infective exacerbation of bronchiectasis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Infective exacerbation of chronic obstructive airways disease | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Influenza | 2/636 (0.3%) | 2 | 1/615 (0.2%) | 1 |
| Laryngitis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Lower respiratory tract infection | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Lung abscess | 1/636 (0.2%) | 1 | 2/615 (0.3%) | 2 |
| Lung infection | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 2 |
| Neutropenic sepsis | 0/636 (0%) | 0 | 2/615 (0.3%) | 2 |
| Oesophageal candidiasis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Peritonitis | 0/636 (0%) | 0 | 2/615 (0.3%) | 2 |
| Pleural infection | 1/636 (0.2%) | 2 | 0/615 (0%) | 0 |
| Pneumocystis jirovecii pneumonia | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Pneumonia | 47/636 (7.4%) | 51 | 32/615 (5.2%) | 38 |
| Pneumonia bacterial | 3/636 (0.5%) | 3 | 2/615 (0.3%) | 2 |
| Pneumonia klebsiella | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Post procedural cellulitis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Pulmonary sepsis | 1/636 (0.2%) | 1 | 2/615 (0.3%) | 2 |
| Respiratory tract infection | 1/636 (0.2%) | 1 | 2/615 (0.3%) | 2 |
| Sepsis | 4/636 (0.6%) | 4 | 2/615 (0.3%) | 3 |
| Septic shock | 2/636 (0.3%) | 2 | 3/615 (0.5%) | 3 |
| Upper respiratory tract infection | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Urinary tract infection | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Vascular access site infection | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Viral infection | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Klebsiella infection | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Cervical vertebral fracture | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Femur fracture | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Hip fracture | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Infusion related reaction | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Lumbar vertebral fracture | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Radius fracture | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Upper limb fracture | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase increased | 3/636 (0.5%) | 3 | 2/615 (0.3%) | 2 |
| Aspartate aminotransferase increased | 3/636 (0.5%) | 3 | 1/615 (0.2%) | 1 |
| Blood bilirubin increased | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Blood calcium decreased | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Blood pressure increased | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Blood prolactin increased | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Neutrophil count decreased | 0/636 (0%) | 0 | 4/615 (0.7%) | 4 |
| Platelet count decreased | 0/636 (0%) | 0 | 2/615 (0.3%) | 3 |
| Urine output decreased | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 3/636 (0.5%) | 3 | 3/615 (0.5%) | 3 |
| Dehydration | 1/636 (0.2%) | 1 | 2/615 (0.3%) | 2 |
| Diabetes mellitus | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Electrolyte imbalance | 0/636 (0%) | 0 | 2/615 (0.3%) | 2 |
| Hypercalcaemia | 3/636 (0.5%) | 3 | 2/615 (0.3%) | 2 |
| Hyperkalaemia | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Hyperuricaemia | 0/636 (0%) | 0 | 2/615 (0.3%) | 3 |
| Hypoglycaemia | 1/636 (0.2%) | 1 | 2/615 (0.3%) | 2 |
| Hyponatraemia | 3/636 (0.5%) | 3 | 1/615 (0.2%) | 1 |
| Ketoacidosis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Type 2 diabetes mellitus | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Back pain | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Myalgia | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Neck pain | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Osteitis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Osteoporotic fracture | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Pain in extremity | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Rotator cuff syndrome | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Adenocarcinoma gastric | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Anogenital warts | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Gastric cancer | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Infected neoplasm | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Keratoacanthoma | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Lung cancer metastatic | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Malignant neoplasm progression | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Metastases to bone | 2/636 (0.3%) | 3 | 0/615 (0%) | 0 |
| Oesophageal carcinoma | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Squamous cell carcinoma | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Squamous cell carcinoma of the tongue | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Tumour necrosis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Malignant pleural effusion | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Metastases to central nervous system | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Neoplasm malignant | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Tumour embolism | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Nervous system disorders | ||||
| Altered state of consciousness | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Ataxia | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Cerebral infarction | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Cerebral ischaemia | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Cerebrovascular accident | 2/636 (0.3%) | 2 | 3/615 (0.5%) | 3 |
| Coma | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Dizziness | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Embolic stroke | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Encephalopathy | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Epilepsy | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Headache | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Ischaemic stroke | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Loss of consciousness | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Metabolic encephalopathy | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Neuropathy peripheral | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Seizure | 1/636 (0.2%) | 1 | 2/615 (0.3%) | 3 |
| Spinal cord compression | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Syncope | 0/636 (0%) | 0 | 2/615 (0.3%) | 2 |
| Transient ischaemic attack | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Brain injury | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Hemiparesis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Psychiatric disorders | ||||
| Completed suicide | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Confusional state | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Delirium | 2/636 (0.3%) | 2 | 2/615 (0.3%) | 2 |
| Depression | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Agitation | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Mental disorder | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 3/636 (0.5%) | 3 | 2/615 (0.3%) | 2 |
| Glomerulonephritis membranous | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Hydronephrosis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Nephritis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Nephropathy | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Renal failure | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Renal tubular necrosis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Urinary retention | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Reproductive system and breast disorders | ||||
| Ovarian cyst torsion | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Acute respiratory failure | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Asthma | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Atelectasis | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Bronchitis chronic | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Chronic obstructive pulmonary disease | 3/636 (0.5%) | 4 | 5/615 (0.8%) | 5 |
| Chronic respiratory failure | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Dyspnoea | 8/636 (1.3%) | 9 | 2/615 (0.3%) | 2 |
| Haemoptysis | 7/636 (1.1%) | 8 | 1/615 (0.2%) | 1 |
| Hydrothorax | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Interstitial lung disease | 4/636 (0.6%) | 6 | 1/615 (0.2%) | 1 |
| Lung disorder | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Oesophagobronchial fistula | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Pleural effusion | 14/636 (2.2%) | 16 | 5/615 (0.8%) | 7 |
| Pleurisy | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Pneumonia aspiration | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Pneumonitis | 25/636 (3.9%) | 26 | 1/615 (0.2%) | 1 |
| Pneumothorax | 3/636 (0.5%) | 3 | 1/615 (0.2%) | 1 |
| Pulmonary artery thrombosis | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Pulmonary embolism | 15/636 (2.4%) | 15 | 11/615 (1.8%) | 11 |
| Pulmonary fistula | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Pulmonary haemorrhage | 4/636 (0.6%) | 4 | 2/615 (0.3%) | 2 |
| Pulmonary oedema | 1/636 (0.2%) | 1 | 2/615 (0.3%) | 2 |
| Pulmonary thrombosis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Respiratory distress | 0/636 (0%) | 0 | 2/615 (0.3%) | 2 |
| Respiratory failure | 4/636 (0.6%) | 4 | 4/615 (0.7%) | 4 |
| Tracheal stenosis | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Drug eruption | 0/636 (0%) | 0 | 1/615 (0.2%) | 2 |
| Rash | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Rash maculo-papular | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Vascular disorders | ||||
| Aortic aneurysm | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Arterial thrombosis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Deep vein thrombosis | 1/636 (0.2%) | 1 | 1/615 (0.2%) | 1 |
| Embolism | 2/636 (0.3%) | 2 | 0/615 (0%) | 0 |
| Hypertension | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Hypotension | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Jugular vein thrombosis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Peripheral artery occlusion | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Peripheral ischaemia | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Superior vena cava syndrome | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Venous thrombosis | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
| Hypovolaemic shock | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Poor venous access | 1/636 (0.2%) | 1 | 0/615 (0%) | 0 |
| Venous thrombosis limb | 0/636 (0%) | 0 | 1/615 (0.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Pembrolizumab | Chemotherapy (SOC Treatment) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 527/636 (82.9%) | 576/615 (93.7%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 97/636 (15.3%) | 118 | 248/615 (40.3%) | 317 |
| Leukopenia | 10/636 (1.6%) | 18 | 35/615 (5.7%) | 63 |
| Neutropenia | 5/636 (0.8%) | 7 | 84/615 (13.7%) | 175 |
| Thrombocytopenia | 5/636 (0.8%) | 6 | 55/615 (8.9%) | 82 |
| Endocrine disorders | ||||
| Hyperthyroidism | 38/636 (6%) | 38 | 4/615 (0.7%) | 4 |
| Hypothyroidism | 76/636 (11.9%) | 95 | 9/615 (1.5%) | 9 |
| Gastrointestinal disorders | ||||
| Constipation | 76/636 (11.9%) | 96 | 130/615 (21.1%) | 166 |
| Diarrhoea | 72/636 (11.3%) | 90 | 74/615 (12%) | 102 |
| Nausea | 71/636 (11.2%) | 95 | 195/615 (31.7%) | 398 |
| Stomatitis | 16/636 (2.5%) | 18 | 33/615 (5.4%) | 40 |
| Vomiting | 49/636 (7.7%) | 59 | 106/615 (17.2%) | 164 |
| General disorders | ||||
| Asthenia | 66/636 (10.4%) | 90 | 79/615 (12.8%) | 108 |
| Chest pain | 52/636 (8.2%) | 57 | 44/615 (7.2%) | 53 |
| Fatigue | 100/636 (15.7%) | 125 | 125/615 (20.3%) | 186 |
| Malaise | 16/636 (2.5%) | 16 | 33/615 (5.4%) | 50 |
| Oedema peripheral | 31/636 (4.9%) | 32 | 34/615 (5.5%) | 44 |
| Pyrexia | 63/636 (9.9%) | 81 | 47/615 (7.6%) | 58 |
| Infections and infestations | ||||
| Pneumonia | 33/636 (5.2%) | 34 | 24/615 (3.9%) | 27 |
| Upper respiratory tract infection | 40/636 (6.3%) | 50 | 31/615 (5%) | 38 |
| Investigations | ||||
| Alanine aminotransferase increased | 62/636 (9.7%) | 82 | 73/615 (11.9%) | 96 |
| Aspartate aminotransferase increased | 60/636 (9.4%) | 79 | 58/615 (9.4%) | 85 |
| Blood alkaline phosphatase increased | 39/636 (6.1%) | 48 | 30/615 (4.9%) | 35 |
| Neutrophil count decreased | 7/636 (1.1%) | 7 | 87/615 (14.1%) | 212 |
| Platelet count decreased | 5/636 (0.8%) | 5 | 63/615 (10.2%) | 133 |
| Weight decreased | 64/636 (10.1%) | 68 | 45/615 (7.3%) | 46 |
| White blood cell count decreased | 6/636 (0.9%) | 8 | 72/615 (11.7%) | 213 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 108/636 (17%) | 126 | 131/615 (21.3%) | 205 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 55/636 (8.6%) | 62 | 74/615 (12%) | 144 |
| Back pain | 61/636 (9.6%) | 68 | 43/615 (7%) | 51 |
| Musculoskeletal pain | 41/636 (6.4%) | 50 | 27/615 (4.4%) | 33 |
| Myalgia | 32/636 (5%) | 36 | 70/615 (11.4%) | 135 |
| Pain in extremity | 30/636 (4.7%) | 34 | 33/615 (5.4%) | 39 |
| Nervous system disorders | ||||
| Dizziness | 23/636 (3.6%) | 25 | 37/615 (6%) | 44 |
| Headache | 44/636 (6.9%) | 55 | 51/615 (8.3%) | 61 |
| Neuropathy peripheral | 5/636 (0.8%) | 6 | 52/615 (8.5%) | 61 |
| Peripheral sensory neuropathy | 4/636 (0.6%) | 5 | 43/615 (7%) | 55 |
| Psychiatric disorders | ||||
| Insomnia | 33/636 (5.2%) | 37 | 44/615 (7.2%) | 50 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 99/636 (15.6%) | 114 | 65/615 (10.6%) | 71 |
| Dyspnoea | 99/636 (15.6%) | 114 | 68/615 (11.1%) | 77 |
| Haemoptysis | 42/636 (6.6%) | 57 | 21/615 (3.4%) | 23 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 3/636 (0.5%) | 4 | 138/615 (22.4%) | 139 |
| Pruritus | 62/636 (9.7%) | 77 | 18/615 (2.9%) | 19 |
| Rash | 68/636 (10.7%) | 77 | 42/615 (6.8%) | 50 |
| Vascular disorders | ||||
| Hypertension | 37/636 (5.8%) | 43 | 13/615 (2.1%) | 16 |
Limitations/Caveats
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 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
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme LLC |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
- 3475-042
- 152877
- MK-3475-042
- KEYNOTE-042
- 2014-001473-14