Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
Conditions
Keywords
Gastric cancer, Gastroesophageal junction cancer, PD1, PD-1, PDL1, PD-L1
Brief summary
This is a study for participants with advanced gastric or gastroesophageal junction adenocarcinoma who have had tumor progression after first-line treatment with platinum and fluoropyrimidine doublet therapy. The primary study hypotheses are that pembrolizumab (MK-3475) prolongs progression free survival (PFS) and overall survival (OS) for participants with tumors that show positive programmed cell death ligand 1 (PD-L1) expression. As of 20-March-2016, enrollment will be limited to PD-L1 positive participants.
Interventions
BIOLOGICALpembrolizumab
200 mg administered as IV infusion on Day 1 of each 21-day cycle.
DRUGpaclitaxel
80 mg/m\^2 administered as IV infusion on Days 1, 8, and 15 of each 28-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 gastric or gastroesophageal junction adenocarcinoma * Confirmed metastatic or locally advanced, unresectable disease (by computed tomography \[CT\] scan or clinical evidence) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Progression on or after prior first-line therapy containing any platinum/fluoropyrimidine doublet * Willing to provide tumor tissue for PD-L1 biomarker analysis (new or archived specimens with agreement of Sponsor). As of 20 March 2016, participants must be PD-L1 positive to be enrolled. * Human epidermal growth factor receptor 2 (HER-2/neu) status known and participants with HER2/neu positive tumors show documentation of disease progression on treatment containing trastuzumab * Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity 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. * Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel. * Adequate organ function
Exclusion criteria
* Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of medication * Squamous cell or undifferentiated gastric cancer * Active autoimmune disease that has required systemic treatment in past 2 years (replacement therapy is not considered a form of systemic treatment * Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication * Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from AEs due to agents administered more than 4 weeks earlier * Prior 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 or surgery * Known additional malignancy that is progressing or requires active treatment (with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy) * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis * History of (noninfectious) 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 trial * Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel. * Prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) clinical trial * Known history of human immunodeficiency virus (HIV) * Known active Hepatitis B or Hepatitis C * Live vaccine within 30 days of planned start of study therapy * Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval \[CI\]) in months was reported for PD-L1 positive participants by treatment group. |
| Overall Survival (OS) in PD-L1 Positive Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was analyzed using the Kaplan-Meier method and median OS (95% CI) in months was reported for PD-L1 positive participants by treatment group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for PD-L1 positive participants by treatment group. |
| PFS According to RECIST 1.1 Based on Investigator Assessment in All Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group. |
| PFS According to Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) Based on BICR in PD-L1 Positive Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | PFS defined as time from randomization to first documented PD per irRECIST based on BICR, or death due to any cause, whichever occurs first. Following initial PD by RECIST 1.1 (20% relative increase in SOD of target lesions), participants were assessed according to irRECIST: tumor assessment was repeated ≥4 weeks later to confirm PD with the option of continuing treatment until this scan was obtained for clinically stable participants. If PD confirmed, participant was discontinued from treatment unless investigator determined benefit. If repeat scan indicated stable disease (SD; neither sufficient shrinkage or increase of target lesion), partial response (PR; ≥30% decrease in the SOD of target lesions), or complete response (CR; disappearance of all non-nodal target lesions), participant could continue treatment at investigator's discretion. PFS analyzed using Kaplan-Meier method and median PFS (95% CI) in months was reported for PD-L1 positive participants by treatment group. |
| PFS According to irRECIST Based on BICR in All Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | PFS defined as time from randomization to first documented PD per irRECIST based on BICR, or death due to any cause, whichever occurs first. Following initial PD by RECIST 1.1 (20% relative increase in SOD of target lesions), participants were assessed according to irRECIST: tumor assessment was repeated ≥4 weeks later to confirm PD with the option of continuing treatment until this scan was obtained for clinically stable participants. If PD confirmed, participant was discontinued from treatment unless investigator determined benefit. If repeat scan indicated SD (neither sufficient shrinkage or increase of target lesion), PR (≥30% decrease in the SOD of target lesions), or CR (disappearance of all non-nodal target lesions), participant could continue treatment at investigator's discretion. PFS analyzed using Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group. |
| Time to Tumor Progression (TTP) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for PD-L1 positive participants by treatment group. |
| TTP According to RECIST 1.1 Based on BICR in All Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for all participants by treatment group. |
| TTP According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for PD-L1 positive participants by treatment group. |
| TTP According to RECIST 1.1 Based on Investigator Assessment in All Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for all participants by treatment group. |
| Objective Response Rate (ORR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for PD-L1 positive participants by treatment group. |
| ORR According to RECIST 1.1 Based on BICR in All Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for all participants by treatment group. |
| PFS According to RECIST 1.1 Based on BICR in All Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group. |
| ORR According to RECIST 1.1 Based on Investigator Assessment in All Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for all participants by treatment group. |
| Duration of Response (DOR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | For PD-L1 positive participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for PD-L1 positive participants with response by treatment group. |
| DOR According to RECIST 1.1 Based on BICR in All Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | For participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for all participants with response by treatment group. |
| DOR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | For PD-L1 positive participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for PD-L1 positive participants with response by treatment group. |
| DOR According to RECIST 1.1 Based on Investigator Assessment in All Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | For participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for all participants with response by treatment group. |
| Percentage of PD-L1 Positive Participants Who Experienced an Adverse Event (AE) | Up to 71 months (through database cut-off date of 10 Jun 2021) | 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 percentage of participants with at least one AE was reported for PD-L1 positive participants by treatment group. |
| Percentage of All Participants Who Experienced an AE | Up to 71 months (through database cut-off date of 10 Jun 2021) | 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 percentage of participants with at least one AE was reported for all participants by treatment group. |
| Percentage of PD-L1 Positive Participants That Discontinued Study Treatment Due to AE | Up to approximately 26.4 months | 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 percentage of participants that discontinued study treatment due to an AE was reported for PD-L1 positive participants by treatment group. |
| Percentage of All Participants That Discontinued Study Treatment Due to AE | Up to approximately 26.4 months | 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 percentage of participants that discontinued study treatment due to an AE was reported for all participants by treatment group. |
| ORR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for PD-L1 positive participants by treatment group. |
| OS in All Participants | Up to 30 months (through database cut-off date of 26 Oct 2017) | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was analyzed using the Kaplan-Meier method and median OS (95% CI) in months was reported for all participants by treatment group. |
Participant flow
Recruitment details
After 20 March 2016, enrollment was limited to programmed cell death ligand 1 (PD-L1) positive participants.
Pre-assignment details
Of 592 participants that were randomized to trial, 570 received treatment. At the time of the primary analysis data cut-off, 89 participants are ongoing in the study.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Participants receive 200 mg IV pembrolizumab on Day 1 of each 21-day cycle, for up to 35 administrations (approximately 2 years). | 296 |
| Paclitaxel Participants receive paclitaxel 80 mg/m\^2 IV, on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity. | 296 |
| Total | 592 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 8 |
| Overall Study | Death | 263 | 265 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Sponsor's decision | 15 | 9 |
| Overall Study | Withdrawal by Subject | 7 | 12 |
Baseline characteristics
| Characteristic | Pembrolizumab | Paclitaxel | Total |
|---|---|---|---|
| Age, Continuous | 60.7 Years STANDARD_DEVIATION 12 | 59.6 Years STANDARD_DEVIATION 11.7 | 60.2 Years STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 24 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 269 Participants | 272 Participants | 541 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| PD-L1 Status Negative | 99 Participants | 96 Participants | 195 Participants |
| PD-L1 Status Positive | 196 Participants | 199 Participants | 395 Participants |
| PD-L1 Status Unknown | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 93 Participants | 91 Participants | 184 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 193 Participants | 198 Participants | 391 Participants |
| Region of Enrollment Asia | 88 Participants | 89 Participants | 177 Participants |
| Region of Enrollment Europe/Israel/North America/Australia | 190 Participants | 187 Participants | 377 Participants |
| Region of Enrollment Rest of World | 18 Participants | 20 Participants | 38 Participants |
| Sex: Female, Male Female | 94 Participants | 88 Participants | 182 Participants |
| Sex: Female, Male Male | 202 Participants | 208 Participants | 410 Participants |
| Time To Progression (TTP) on first-line therapy <6 months | 186 Participants | 182 Participants | 368 Participants |
| Time To Progression (TTP) on first-line therapy ≥6 months | 110 Participants | 114 Participants | 224 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 278 / 296 | 287 / 296 | 2 / 3 |
| other Total, other adverse events | 256 / 294 | 260 / 276 | 3 / 3 |
| serious Total, serious adverse events | 108 / 294 | 68 / 276 | 1 / 3 |
Outcome results
Primary
Overall Survival (OS) in PD-L1 Positive Participants
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was analyzed using the Kaplan-Meier method and median OS (95% CI) in months was reported for PD-L1 positive participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized PD-L1 positive participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival (OS) in PD-L1 Positive Participants | 9.1 months |
| Paclitaxel | Overall Survival (OS) in PD-L1 Positive Participants | 8.3 months |
Comparison: Treatment difference in OS was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (HR) between the treatment arms.p-value: 0.0420595% CI: [0.66, 1.03]Regression, Cox
Primary
Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval \[CI\]) in months was reported for PD-L1 positive participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized PD-L1 positive participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants | 1.5 months |
| Paclitaxel | Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants | 4.1 months |
Comparison: Treatment difference in PFS was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (Hazard Ratio \[HR\]) between the treatment arms.p-value: 0.9835895% CI: [1.03, 1.57]Regression, Cox
Secondary
DOR According to RECIST 1.1 Based on BICR in All Participants
For participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for all participants with response by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: The subset of all randomized participants that showed a CR or PR according to RECIST 1.1 and based on BICR. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | DOR According to RECIST 1.1 Based on BICR in All Participants | 18.0 months |
| Paclitaxel | DOR According to RECIST 1.1 Based on BICR in All Participants | 5.5 months |
Secondary
DOR According to RECIST 1.1 Based on Investigator Assessment in All Participants
For participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for all participants with response by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: The subset of all randomized participants that showed a CR or PR according to RECIST 1.1 and based on investigator assessment. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | DOR According to RECIST 1.1 Based on Investigator Assessment in All Participants | 15.7 months |
| Paclitaxel | DOR According to RECIST 1.1 Based on Investigator Assessment in All Participants | 4.3 months |
Secondary
DOR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
For PD-L1 positive participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for PD-L1 positive participants with response by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: The subset of all randomized PD-L1 positive participants that showed a CR or PR according to RECIST 1.1 and based on investigator assessment. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | DOR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | 15.7 months |
| Paclitaxel | DOR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | 4.3 months |
Secondary
Duration of Response (DOR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
For PD-L1 positive participants who demonstrated CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. DOR was analyzed using the Kaplan-Meier method and median DOR (range) in months was reported for PD-L1 positive participants with response by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: The subset of all randomized PD-L1 positive participants that showed a CR or PR according to RECIST 1.1 and based on BICR. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Duration of Response (DOR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants | 18.0 months |
| Paclitaxel | Duration of Response (DOR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants | 5.2 months |
Secondary
Objective Response Rate (ORR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for PD-L1 positive participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized PD-L1 positive participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Objective Response Rate (ORR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants | 15.8 Percentage of participants |
| Paclitaxel | Objective Response Rate (ORR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants | 13.6 Percentage of participants |
Comparison: Stratified Miettinen and Nurminen's (MN) method was used for comparison of the ORR between the treatment arms. A 95% CI for the difference in response rates between the pembrolizumab arm and paclitaxel arm was provided.p-value: 0.2896795% CI: [-5, 9.1]Miettinen and Nurminen method
Secondary
ORR According to RECIST 1.1 Based on BICR in All Participants
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for all participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | ORR According to RECIST 1.1 Based on BICR in All Participants | 11.1 Percentage of participants |
| Paclitaxel | ORR According to RECIST 1.1 Based on BICR in All Participants | 12.5 Percentage of participants |
Comparison: Stratified MN method was used for comparison of the ORR between the treatment arms. A 95% CI for the difference in response rates between the pembrolizumab arm and paclitaxel arm was provided.p-value: 0.690195% CI: [-6.5, 4]Miettinen and Nurminen method
Secondary
ORR According to RECIST 1.1 Based on Investigator Assessment in All Participants
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for all participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | ORR According to RECIST 1.1 Based on Investigator Assessment in All Participants | 12.2 Percentage of participants |
| Paclitaxel | ORR According to RECIST 1.1 Based on Investigator Assessment in All Participants | 15.2 Percentage of participants |
Comparison: Stratified Miettinen and Nurminen's method was used for comparison of the ORR between the treatment arms. A 95% CI for the difference in response rates between the pembrolizumab arm and paclitaxel arm is provided.p-value: 0.8592295% CI: [-8.5, 2.6]Miettinen and Nurminen method
Secondary
ORR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
ORR was defined as the percentage of the participants in the analysis population who had a confirmed CR (disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on investigator assessment. ORR was analyzed using the stratified Miettinen and Nurminen method, and reported with 95% CI for PD-L1 positive participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized PD-L1 positive participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | ORR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | 17.3 Percentage of participants |
| Paclitaxel | ORR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | 15.6 Percentage of participants |
Comparison: Stratified MN method was used for comparison of the ORR between the treatment arms. A 95% CI for the difference in response rates between the pembrolizumab arm and paclitaxel arm was provided.p-value: 0.332295% CI: [-5.8, 9.1]Miettinen and Nurminen method
Secondary
OS in All Participants
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was analyzed using the Kaplan-Meier method and median OS (95% CI) in months was reported for all participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | OS in All Participants | 6.7 months |
| Paclitaxel | OS in All Participants | 8.3 months |
Comparison: Treatment difference in OS was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (Hazard Ratio \[HR\]) between the treatment arms.p-value: 0.2446395% CI: [0.79, 1.12]Regression, Cox
Secondary
Percentage of All Participants That Discontinued Study Treatment Due to 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 percentage of participants that discontinued study treatment due to an AE was reported for all participants by treatment group.
Time frame: Up to approximately 26.4 months
Population: All randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Percentage of All Participants That Discontinued Study Treatment Due to AE | 4.8 Percentage of participants |
| Paclitaxel | Percentage of All Participants That Discontinued Study Treatment Due to AE | 9.1 Percentage of participants |
Secondary
Percentage of All Participants Who Experienced an 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 percentage of participants with at least one AE was reported for all participants by treatment group.
Time frame: Up to 71 months (through database cut-off date of 10 Jun 2021)
Population: All randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Percentage of All Participants Who Experienced an AE | 93.9 Percentage of participants |
| Paclitaxel | Percentage of All Participants Who Experienced an AE | 97.1 Percentage of participants |
Comparison: Between-treatment differences (Pembrolizumab vs. Paclitaxel) in the percentage of participants with events and accompanying 95% confidence intervals were based on the Miettinen and Nurminen method. Negative values correspond to a greater percentage of events for Paclitaxel.95% CI: [-6.9, 0.2]
Secondary
Percentage of PD-L1 Positive Participants That Discontinued Study Treatment Due to 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 percentage of participants that discontinued study treatment due to an AE was reported for PD-L1 positive participants by treatment group.
Time frame: Up to approximately 26.4 months
Population: All randomized PD-L1 positive participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Percentage of PD-L1 Positive Participants That Discontinued Study Treatment Due to AE | 4.1 Percentage of participants |
| Paclitaxel | Percentage of PD-L1 Positive Participants That Discontinued Study Treatment Due to AE | 8.0 Percentage of participants |
Secondary
Percentage of PD-L1 Positive Participants Who Experienced 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 percentage of participants with at least one AE was reported for PD-L1 positive participants by treatment group.
Time frame: Up to 71 months (through database cut-off date of 10 Jun 2021)
Population: All randomized PD-L1 positive participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Percentage of PD-L1 Positive Participants Who Experienced an Adverse Event (AE) | 93.3 Percentage of participants |
| Paclitaxel | Percentage of PD-L1 Positive Participants Who Experienced an Adverse Event (AE) | 97.3 Percentage of participants |
Secondary
PFS According to Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) Based on BICR in PD-L1 Positive Participants
PFS defined as time from randomization to first documented PD per irRECIST based on BICR, or death due to any cause, whichever occurs first. Following initial PD by RECIST 1.1 (20% relative increase in SOD of target lesions), participants were assessed according to irRECIST: tumor assessment was repeated ≥4 weeks later to confirm PD with the option of continuing treatment until this scan was obtained for clinically stable participants. If PD confirmed, participant was discontinued from treatment unless investigator determined benefit. If repeat scan indicated stable disease (SD; neither sufficient shrinkage or increase of target lesion), partial response (PR; ≥30% decrease in the SOD of target lesions), or complete response (CR; disappearance of all non-nodal target lesions), participant could continue treatment at investigator's discretion. PFS analyzed using Kaplan-Meier method and median PFS (95% CI) in months was reported for PD-L1 positive participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized PD-L1 positive participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | PFS According to Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) Based on BICR in PD-L1 Positive Participants | 1.9 months |
| Paclitaxel | PFS According to Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) Based on BICR in PD-L1 Positive Participants | 4.2 months |
Comparison: Treatment difference in PFS was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (HR) between the treatment arms.p-value: 0.8069695% CI: [0.89, 1.38]Regression, Cox
Secondary
PFS According to irRECIST Based on BICR in All Participants
PFS defined as time from randomization to first documented PD per irRECIST based on BICR, or death due to any cause, whichever occurs first. Following initial PD by RECIST 1.1 (20% relative increase in SOD of target lesions), participants were assessed according to irRECIST: tumor assessment was repeated ≥4 weeks later to confirm PD with the option of continuing treatment until this scan was obtained for clinically stable participants. If PD confirmed, participant was discontinued from treatment unless investigator determined benefit. If repeat scan indicated SD (neither sufficient shrinkage or increase of target lesion), PR (≥30% decrease in the SOD of target lesions), or CR (disappearance of all non-nodal target lesions), participant could continue treatment at investigator's discretion. PFS analyzed using Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | PFS According to irRECIST Based on BICR in All Participants | 1.6 months |
| Paclitaxel | PFS According to irRECIST Based on BICR in All Participants | 4.2 months |
Comparison: Treatment difference in PFS was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (HR) between the treatment arms.p-value: 0.9993295% CI: [1.12, 1.6]Regression, Cox
Secondary
PFS According to RECIST 1.1 Based on BICR in All Participants
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | PFS According to RECIST 1.1 Based on BICR in All Participants | 1.5 months |
| Paclitaxel | PFS According to RECIST 1.1 Based on BICR in All Participants | 4.1 months |
Comparison: Treatment difference in PFS was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (Hazard Ratio \[HR\]) between the treatment arms.p-value: 0.9999995% CI: [1.25, 1.77]Regression, Cox
Secondary
PFS According to RECIST 1.1 Based on Investigator Assessment in All Participants
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for all participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | PFS According to RECIST 1.1 Based on Investigator Assessment in All Participants | 1.6 months |
| Paclitaxel | PFS According to RECIST 1.1 Based on Investigator Assessment in All Participants | 3.2 months |
Comparison: Treatment difference in PFS was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (HR) between the treatment arms.p-value: 0.9748195% CI: [1, 1.42]Regression, Cox
Secondary
PFS According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment, or death due to any cause, whichever occurs first. According to RECIST 1.1, PD was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% CI) in months was reported for PD-L1 positive participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized PD-L1 positive participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | PFS According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | 1.6 months |
| Paclitaxel | PFS According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | 3.1 months |
Comparison: Treatment difference in PFS was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (HR) between the treatment arms.p-value: 0.4133195% CI: [0.79, 1.21]Regression, Cox
Secondary
Time to Tumor Progression (TTP) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for PD-L1 positive participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized PD-L1 positive participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Time to Tumor Progression (TTP) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants | 1.6 months |
| Paclitaxel | Time to Tumor Progression (TTP) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants | 4.0 months |
Comparison: Treatment difference in TTP was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (HR) between the treatment arms.p-value: 0.9966195% CI: [1.11, 1.89]Regression, Cox
Secondary
TTP According to RECIST 1.1 Based on BICR in All Participants
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for all participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | TTP According to RECIST 1.1 Based on BICR in All Participants | 1.5 months |
| Paclitaxel | TTP According to RECIST 1.1 Based on BICR in All Participants | 4.1 months |
Comparison: Treatment difference in TTP was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (HR) between the treatment arms.p-value: 195% CI: [1.42, 2.2]Regression, Cox
Secondary
TTP According to RECIST 1.1 Based on Investigator Assessment in All Participants
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for all participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | TTP According to RECIST 1.1 Based on Investigator Assessment in All Participants | 1.6 months |
| Paclitaxel | TTP According to RECIST 1.1 Based on Investigator Assessment in All Participants | 3.8 months |
Comparison: Treatment difference in TTP was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (HR) between the treatment arms.p-value: 0.9703395% CI: [1, 1.47]Regression, Cox
Secondary
TTP According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator assessment. Using RECIST 1.1, progressive disease was defined as a 20% relative increase in the SOD of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. TTP was analyzed using the Kaplan-Meier method and median TTP (95% CI) in months was reported for PD-L1 positive participants by treatment group.
Time frame: Up to 30 months (through database cut-off date of 26 Oct 2017)
Population: All randomized PD-L1 positive participants. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | TTP According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | 2.1 months |
| Paclitaxel | TTP According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants | 3.3 months |
Comparison: Treatment difference in TTP was assessed by the Stratified Log-rank test, and a stratified Cox proportional hazard model with Efron's method of tie handling was used to assess the magnitude of the treatment difference (HR) between the treatment arms.p-value: 0.392895% CI: [0.77, 1.23]Regression, Cox