KEYTRUDA® in the first-line setting for metastatic non-small cell lung cancer (NSCLC)1
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EXPLORE KEYTRUDA® in the KEYNOTE-024 trial for patients with metastatic NSCLC and PD-L1 TPS≥50%
KEYNOTE-024 trial: Controlled, open-label trial of treatment-naïve patients with metastatic NSCLC
Trial overview
- Multicenter, open-label, randomized, controlled trial
- Encompassing 305 patients
- Key eligibility criteria were PD-L1 expression tumour proportion score (TPS) of 50% or greater and no prior systemic treatment for metastatic NSCLC
Treatment arms
KEYTRUDA® 200 mg Q3W or
Chemotherapy regimen, choice at the discretion of the treating physician. Regimens included:
- Pemetrexed 500 mg/m2 Q3W and carboplatin AUC 5 to 6 mg/mL/min Q3W on Day 1 for 4 to 6 cycles followed by optional pemetrexed 500 mg/m2 Q3W for patients with non-squamous histologies
- Pemetrexed 500 mg/m2 Q3W and cisplatin 75 mg/m2 Q3W on Day 1 for 4 to 6 cycles followed by optional pemetrexed 500 mg/m2 every Q3W for patients with non-squamous histologies
- Gemcitabine 1250 mg/m2 on Days 1 and 8 and cisplatin 75 mg/m2 Q3W on Day 1 for 4 to 6 cycles
- Gemcitabine 1250 mg/m2 on Days 1 and 8 and carboplatin AUC 5 to 6 mg/mL/min Q3W on Day 1 for 4 to 6 cycles
- Paclitaxel 200 mg/m2 Q3W and carboplatin AUC 5 to 6 mg/mL/min Q3W on Day 1 for 4 to 6 cycles followed by optional pemetrexed maintenance (for non-squamous histologies)
Primary endpoints
- Progression-free survival, as assessed by BICR using RECIST 1.1
Key secondary endpoints
- Overall survival
Secondary endpoints
- Objective response rate, as assessed by BICR using RECIST 1.1
AE=adverse management; AUC=area under the concentration; BICR=blinded independent central review; HR=hazard ratio; ITT=intent-to-treat; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS=overall survival; PFS= progression-free survival; PD-L1=programmed death ligand 1; RECIST=response evaluation criteria in solid tumours; TPS=tumour proportion score.
* Based on the stratified Cox proportional hazard model
† Based on stratified log-rank testIntent to treat (ITT) population (interim analysis)
Progression Free Survival
Demonstrated improved progression-free survival for patients on KEYTRUDA® vs investigator’s choice of chemotherapy (primary endpoint)
50% reduction in the risk of progression or death with KEYTRUDA® vs. investigator’s choice of chemotherapy, (HR=0.50 [95% CI: 0.37, 0.68; p<0.001†]) for patients with mNSCLC
Progression-Free Survival in the KEYNOTE-024 trial (by treatment arm, intent to treat Population)
Overall survival
Demonstrated significant improvement in the overall survival for patients on KEYTRUDA® vs patients on investigator’s choice of chemotherapy (secondary endpoint)
40% reduction in the instantaneous risk of death with KEYTRUDA® vs. investigator’s choice of chemotherapy, HR=0.60* [95% CI: 0.41, 0.89]; p=0.005†
KEYTRUDA® 200 mg every 3 weeks
n=154Chemotherapy
n=151OS29%42%HR=0.60* [95% CI: 0.41, 0.89]; p=0.005†Objective Response Rate
45% overall response rate for KEYTRUDA® (pembrolizumab) (95% CI: 37, 53) vs. 28% (95% CI: 21, 36) for investigators’ choice of platinum-containing chemotherapy (secondary endpoint)
Intent to treat (ITT) population (final analysis)
Overall survival
Overall survival with KEYTRUDA® vs. investigator’s choice of chemotherapy was HR= 0.63 [95% CI: 0.47, 0.86]
Kaplan-Meier Curve for Overall Survival in the KEYNOTE-024 trial, intent-to-treat population (final analysis)
Median Overall Survival
Median overall survival for patients with KEYTRUDA® vs. investigator’s choice of chemotherapy
Median overall survivalKEYTRUDA®
30 months
(95% CI: 18.3, not reached)Investigator’s choice of chemotherapy
14.2 months
(95% CI: 9.8, 19.0)AE=adverse management; AUC=area under the concentration; BICR=blinded independent central review; HR=hazard ratio; ITT=intent-to-treat; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS=overall survival; PFS= progression-free survival; PD-L1=programmed death ligand 1; RECIST=response evaluation criteria in solid tumours; TPS=tumour proportion score.
* Based on the stratified Cox proportional hazard model
† Based on stratified log-rank testKEYTRUDA® demonstrated safety profile results in metastatic NSCLC in the KEYNOTE-024 trial
The most common Grade 3–5 treatment-related adverse events for patients treated with KEYTRUDA® were:
Adverse ReactionKEYTRUDA® 200 mg Q3W
(n=154)
%Chemotherapy
(n=150)
%Diarrhea3.91.3Pneumonitis2.60.7Anemia1.919.3- Treatment was discontinued for treatment-related adverse events in 7.1% of the 154 patients receiving KEYTRUDA® and in 10.7% of the 150 patients receiving chemotherapy.
- The median time to discontinuation for treatment-related adverse events was 0.7 months.
- There were 9 (5.8%) deaths reported in the KEYTRUDA® arm and 7 (4.7%) deaths in the chemotherapy arm.
- The most common treatment-related adverse events leading to study drug discontinuation (occurring in more than 2 patients) was pneumonitis (n=6).
Treatment-related adverse events, any grade (reported in ≥10% of patients) were:
Adverse ReactionKEYTRUDA® 200 mg Q3W
(n=154)
%Сhemotherapy
(n=150)
%Diarrhea14.313.3Pyrexia10.45.3Fatigue10.428.7Nausea9.743.3Decreased appetite9.126.0Anemia5.244.0Constipation3.911.3Vomiting2.620.0Stomatitis2.612.0Blood creatinine increased1.910.0For the complete list of treatment-related adverse events, please consult the Product Monograph
AE=adverse management; AUC=area under the concentration; BICR=blinded independent central review; HR=hazard ratio; ITT=intent-to-treat; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS=overall survival; PFS= progression-free survival; PD-L1=programmed death ligand 1; RECIST=response evaluation criteria in solid tumours; TPS=tumour proportion score.
* Based on the stratified Cox proportional hazard model
† Based on stratified log-rank test -
EXPLORE KEYTRUDA® in the KEYNOTE-042 trial for patients with stage III NSCLC who were not eligible for surgical radiation or definitive chemoradiation or patients with metastatic NSCLC.
KEYNOTE-042 trial: Controlled trial in patients with unresectable or metastatic NSCLC or stage III NSCLC who were not candidates for surgical resection or definitive chemoradiation
Trial overview
- Multicenter, randomized, controlled trial conducted
- Encompassed 1,274 patients with stage III NSCLC who were not candidates for surgical resection or definitive chemoradiation, or patients with metastatic NSCLC
- Only patients with TPS ≥1% and who had not received prior systemic treatment for metastatic NSCLC were eligible
Treatment arms
KEYTRUDA® 200 mg Q3W
Investigator’s choice platinum-containing chemotherapy, including pemetrexed + carboplatin or paclitaxel + carboplatin. Patients with non-squamous NSCLC could receive pemetrexed maintenance.
Primary endpoints
- Overall survival
Secondary endpoints
- Progression-free survival, as assessed by BICR using RECIST 1.1
- Overall response rate, as assessed by BICR using RECIST 1.1
AE=adverse management; BICR=blinded independent central review; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PD-L1= programmed death ligand 1; PFS= progression-free survival; plat/pem=platinum+pemetrexed; RECIST=response evaluation criteria in solid tumours; TPS=tumor proportion score.
* Based on the stratified Cox proportional hazard model
† Based on stratified log-rank test
§ Not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints.ITT population
Overall Survival
Demonstrated improvement in the overall survival for patients on KEYTRUDA® vs patients on investigator’s choice of chemotherapy (primary endpoint)
18% reduction in the instantaneous risk of death with KEYTRUDA® vs. chemotherapy (HR=0.82* [95% CI: 0.71, 0.93; p=0.0013†])
Kaplan-Meier Curve for Overall Survival by Treatment Arm in the KEYNOTE-042 trial (TPS ≥ 1%, Intent to Treat Population)
Median Overall Survival
Median overall survival for KEYTRUDA® + plat/pem patients vs. placebo + plat/pem patients1
(Primary endpoint)Median overall survivalKEYTRUDA®
16.4 months
(14.0, 19.7)Chemotherapy
12.1 months
(11.3, 13.3)Overall survival in PD-L1 positive patients (subpopulation)
Overall survival with KEYTRUDA® vs chemotherapy
TPS ≥ 50%TPS 1 to 49%KEYTRUDA®
200 mg Q3W
(n=299)Chemotherapy (n=300)KEYTRUDA®
200 mg Q3W
(n=338)Chemotherapy (n=337)OSHR=0.70* (95% CI: 0.58, 0.86)HR=0.91* (95% CI: 0.77, 1.09)60%
of patients with
event73%
of patients with
event72%
of patients with event77%
of patients with eventMedian OS20.0 months
(95% CI: 15.9, 24.2)12.2 months
(95% CI: 10.4, 14.6)13.4 months
(95% CI: 10.7, 16.9)12.1 months
(95% CI: 11.0, 14.0)Objective Response Rate
Objective response rate for KEYTRUDA® + plat/pem patients vs. placebo + plat/pem patients1
(Secondary endpoint)KEYTRUDA® 200 mg Q3W
(n=637)Chemotherapy
(n=637)Objective response rate (95% CI)27% (24,31)27% (23,30)Complete response0.5%vs0.5%Partial response27%vs26%AE=adverse management; BICR=blinded independent central review; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PD-L1= programmed death ligand 1; PFS= progression-free survival; plat/pem=platinum+pemetrexed; RECIST=response evaluation criteria in solid tumours; TPS=tumor proportion score.
* Based on the stratified Cox proportional hazard model
† Based on stratified log-rank test
§ Not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints.KEYTRUDA® demonstrated safety profile results in metastatic NSCLC in the KEYNOTE-042 trial
The most common Grade 3–5 treatment-related adverse events for patients treated with KEYTRUDA® were:
Adverse ReactionKEYTRUDA® 200mg Q3W
(n=636)
%Chemotherapy
(n=615)
%Pneumonitis3.10Alanine aminotransferase increased1.40.9- Treatment was discontinued for treatment-related adverse events in 9.0% of the 636 patients receiving KEYTRUDA® and in 9.4% of the 615 patients receiving chemotherapy.
- The most common treatment-related adverse events leading to study drug discontinuation (occurring in more than 2 patients) were pneumonitis (n=19) alanine aminotransferase increased (n=6), aspartate aminotransferase increased (n=3).
- The median time to discontinuation for treatment-related adverse events was 2.8 months.
Treatment-related adverse events, any grade (reported in ≥10% of patients) were:
Adverse ReactionKEYTRUDA® 200mg Q3W
(n=636)
%Chemotherapy
(n=615)
%Hypothyroidism10.80.3Fatigue7.916.6Decreased appetite6.317.7Anemia5.537.2Nausea4.929.9Vomiting2.415.8Constipation1.311.1For the complete list of treatment-related adverse events, please consult the Product Monograph
AE=adverse management; BICR=blinded independent central review; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PD-L1= programmed death ligand 1; PFS= progression-free survival; plat/pem=platinum+pemetrexed; RECIST=response evaluation criteria in solid tumours; TPS=tumor proportion score.
* Based on the stratified Cox proportional hazard model
† Based on stratified log-rank test
§ Not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints. -
EXPLORE KEYTRUDA® in the KEYNOTE-189 trial for patients with metastatic non-squamous NSCLC
KEYNOTE-189 trial: Active-controlled, double-blind trial in treatment-naïve patients with metastatic non-squamous NSCLC.
Trial overview:
- Multicentre, randomized, active-controlled
- Encompassing 616 patients
Treatment arms
KEYTRUDA® 200 mg with pemetrexed 500 mg/m2 and investigator’s choice of cisplatin 75 mg/m2 or carboplatin AUC 5 mg/mL/min intravenously Q3W for 4 cycles followed by KEYTRUDA® 200 mg and pemetrexed 500 mg/m2 intravenously Q3W
Placebo with pemetrexed 500 mg/m2 and investigator’s choice of cisplatin 75 mg/m2 or carboplatin AUC 5 mg/mL/min intravenously Q3W for 4 cycles followed by placebo and pemetrexed 500 mg/m2 intravenously Q3W
Primary endpoints
- Overall survival
- Progression-free survival, as assessed by BICR using RECIST 1.1
Secondary endpoints
- Objective response rate
- Response duration, as assessed by BICR using RECIST 1.1
AE=adverse management; AUC= area under the concentration; BICR=blinded independent central review; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; mDOR= median duration of response; NA=not available; mPFS= median progression-free survival; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PFS= progression-free survival; plat/pem=platinum+pemetrexed; RECIST=response evaluation criteria in solid tumours.
* Based on the stratified Cox proportional hazard model
† Based on stratified log-rank test
‡ Based on patients with a best overall response as confirmed complete or partial response
#Based on Miettinen and Nurminen method stratified by PD-L1 status, platinum chemotherapy and smoking status
a Based on Kaplan-Meier estimation
b At the initial interim analysis (n=101 for KEYTRUDA® combination therapy, n=102 for placebo), a statistically significant difference was observed; ORR was 58% [95% CI (48, 68)] and 35% [95% CI (26, 45)] for placebo, p=0.0004ITT population (interim analysis)
Overall Survival
Demonstrated improved overall survival for patients on KEYTRUDA® + plat/pem vs. patients on placebo + plat/pem (primary endpoint)
51% reduction in the instantaneous risk of death with KEYTRUDA® vs. Placebo, both in combination with plat/pem, (HR=0.49* [95% CI: 0.38, 0.64; p<0.00001†]) (interim analysis)
KEYTRUDA® + Pemetrexed + Platinum Chemotherapy n=410Placebo + Pemetrexed + Platinum Chemotherapy n=206OS31%52%HR=0.49* [95% CI: 0.38, 0.64; p<0.00001†Median Overall Survival
Median overall survival for patients on KEYTRUDA® + plat/pem vs. patients on placebo + plat/pem (primary endpoint, interim analysis)
Median overall survivalKEYTRUDA® + plat/pem
Not reached (95%CI: NA, NA)Placebo + plat/pem
11.3 months (95% CI: 8.7, 15.1)Progression Free Survival
Progression-free survival for patients on KEYTRUDA® + plat/pem vs. patients on placebo + plat/pem (primary endpoint, interim analysis)
48% reduction in the risk of progression or death demonstrated for KEYTRUDA® + plat/pem patients vs placebo + plat/pem patients HR=0.52* [95% CI: 0.43, 0.64; p<0.00001† ] (primary endpoint)
KEYTRUDA® + plat/pem
n=410Placebo + plat/pem
n=206mPFS†60%81%95% CI: 0.43, 0.64; p<0.00001†8.8 months
(7.6, 9.2)4.9 months
(4.7, 5.5)KEYTRUDA® + plat/pemPlacebo + plat/pemPFS at 6 months66%40%PFS at 9 months48%25%Objective Response Rate
Objective response rate for patients on KEYTRUDA® + plat/pem vs. patients on placebo + plat/pem (primary endpoint, interim analysis)
2.5X higher overall response rate‡a, demonstrated for KEYTRUDA® + plat/pem patients vs placebo + plat/chemb patients (95% CI: 43, 53); p<0.0001# (secondary endpoint)
KEYTRUDA® + plat/pemPlacebo + plat/pemORR48% (43,53)19% (14,25)Complete response0.5%0.5%Partial response47%18%Median Duration of Response
Median duration of response for patients on KEYTRUDA® + plat/pem vs. patients on placebo + plat/pem (secondary endpoint, interim analysis)
KEYTRUDA® + plat/pemPlacebo + plat/pemmDOR11.2 months
(1.1+,18.0+)7.8 months
(2.1+,16.4+)% with DOR ≥6monthsa 81%63%% with DOR ≥9monthsa 59%44%ITT population (final analysis)
Overall Survival
Overall survival for patients with KEYTRUDA® + plat/pem vs Placebo + plat/pem (final analysis)
Overall survival for patients with KEYTRUDA® + plat/pem vs Placebo + plat/pem was HR=0.56 (95% CI: 0.46, 0.69)
Kaplan-Meier Curve for Overall Survival in the KEYNOTE-189 trial, intent-to-treat population (final analysis)
AE=adverse management; AUC= area under the concentration; BICR=blinded independent central review; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; mDOR= median duration of response; NA=not available; mPFS= median progression-free survival; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PFS= progression-free survival; plat/pem=platinum+pemetrexed; RECIST=response evaluation criteria in solid tumours.
* Based on the stratified Cox proportional hazard model
† Based on stratified log-rank test
‡ Based on patients with a best overall response as confirmed complete or partial response
#Based on Miettinen and Nurminen method stratified by PD-L1 status, platinum chemotherapy and smoking status
a Based on Kaplan-Meier estimation
b At the initial interim analysis (n=101 for KEYTRUDA® combination therapy, n=102 for placebo), a statistically significant difference was observed; ORR was 58% [95% CI (48, 68)] and 35% [95% CI (26, 45)] for placebo, p=0.0004KEYTRUDA® demonstrated safety profile results in metastatic NSCLC in the KEYNOTE-189 trial
The most common Grade 3–5 treatment-related adverse events for patients treated with KEYTRUDA® were:
KEYTRUDA® + plat/pem
(n=405)
%Placebo + plat/pem
(n=202)
%Neutropenia14.6%10.9%Anemia13.6%13.4%Thrombocytopenia7.7%6.5%Febrile neutropenia6.0%2.0%- Treatment was discontinued for treatment-related adverse events in 9.6% of the 405 patients receiving KEYTRUDA®, pemetrexed, and chemotherapy and in 4.0% of the 202 patients receiving placebo, pemetrexed, and chemotherapy
- The most common treatment-related adverse events leading to study drug discontinuation (occurring in more than 3 patients) were acute kidney injury (n=7) and pneumonitis (n=7)
- The median time to discontinuation for treatment-related adverse events was 4.0 months.
Treatment-related adverse events, any grade (reported in ≥ 20% of patients) were:
Adverse ReactionKEYTRUDA® + Pemetrexed + Platinum chemotherapy
(n=405)
%Placebo + Pemetrexed + Platinum chemotherapy
(n=202)
%Nausea46.244.6Anemia38.038.1Fatigue33.130.7Neutropenia24.922.3Decreased appetite20.720.8For the complete list of treatment-related adverse events, please consult the Product Monograph
AE=adverse management; AUC= area under the concentration; BICR=blinded independent central review; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; mDOR= median duration of response; NA=not available; mPFS= median progression-free survival; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PFS= progression-free survival; plat/pem=platinum+pemetrexed; RECIST=response evaluation criteria in solid tumours.
* Based on the stratified Cox proportional hazard model
† Based on stratified log-rank test
‡ Based on patients with a best overall response as confirmed complete or partial response
#Based on Miettinen and Nurminen method stratified by PD-L1 status, platinum chemotherapy and smoking status
a Based on Kaplan-Meier estimation
b At the initial interim analysis (n=101 for KEYTRUDA® combination therapy, n=102 for placebo), a statistically significant difference was observed; ORR was 58% [95% CI (48, 68)] and 35% [95% CI (26, 45)] for placebo, p=0.0004 -
Explore KEYTRUDA® in the KEYNOTE-407 trial for patients with squamous metastatic NSCLC
KEYNOTE-407 trial: Multicentre, placebo-controlled trial in patients with metastatic squamous NSCLC
Trial overview
- Randomized, double-blind placebo-controlled trial
- Encompassing 559 patients
Treatment arms
KEYTRUDA® 200 mg and carboplatin AUC 6 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles, and paclitaxel 200 mg/m2 on Day 1 of each 21-day cycle for 4 cycles or nab-paclitaxel 100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle for 4 cycles, followed by KEYTRUDA® 200 mg Q3W
Placebo and carboplatin AUC 6 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles and paclitaxel 200 mg/m2 on Day 1 of each 21-day cycle for 4 cycles or nab-paclitaxel 100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle for 4 cycles, followed by placebo Q3W
Major efficacy endpoints
- Overall survival
- Progression-free survival, as assessed by BICR using RECIST 1.1
- Overall response rate, as assessed by BICR using RECIST 1.1
Additional efficacy endpoints
- Response duration, as assessed by BICR using RECIST 1.1
AE=adverse management; AUC= area under the concentration; BICR=blinded independent central review; carb pac/nab-pac= carboplatin + paclitaxel or + nab-paclitaxel; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; mDOR= median duration of response; mOS= median overall survival; NA=not available; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PD-L1= programmed death ligand 1; PFS= progression-free survival; RECIST=response evaluation criteria in solid tumours; TPS=tumor proportion score
¶Based on the stratified Cox proportional hazard model
*Based on Kaplan-Meier estimation
a ‘+’ indicates there is no progressive disease by the time of last disease assessment
b At the initial interim analysis (n=101 for KEYTRUDA® combination therapy, n=102 for placebo), a statistically significant difference was observed; ORR was 58% [95% CI (48, 68)] and 35% [95% CI (26, 45)] for placebo, p=0.0004ITT population (interim analysis)
Overall Survival
Demonstrated improvement of the overall survival for patients on KEYTRUDA® vs patients on placebo both in combination with carboplatin + paclitaxel or + nab-paclitaxelc1 (interim analysis)
36% reduction¶ in the instantaneous risk of death with KEYTRUDA® vs. placebo both in combination with carb pac/nab-pac1 (HR=0.64 [95% CI: 0.49, 0.85; p=0.0008])
KEYTRUDA® + Carboplatin + Paclitaxel/Nab-Paclitaxel
n=278Placebo + Carboplatin+ Paclitaxel/Nab-Paclitaxel
n=281OS31%43%HR=0.64 [95% CI: 0.49, 0.85; p=0.0008]Median Overall Survival
Median overall survival for patients with KEYTRUDA® + carb pac/nab-pac vs Placebo + carb pac/nab-pac
mOSKEYTRUDA® + carb pac/nab-pac (13.2, NA)Placebo + carb pac/nab-pac (95% CI: 9.5, 14.8)15.9 months11.3 monthsObjective Response Rate
X1.5 objective response rate demonstrated for KEYTRUDA® patients vs. placebo patients, both + pac/nab-pac∊ (Interim analysis, secondary endpoint)
ORRKEYTRUDA® + carb pac/nab-pacPlacebo + carb pac/nab-pac58% (95% CI: 52, 64) p=0.000438% (95% CI: 33, 44)Median duration of response (Interim analysis)
KEYTRUDA® + carb pac/nab-pacPlacebo + carb pac/nab-pacmDORa7.7 months
(range: 1.1+, 14.7+)4.8 months
(range: 1.3+, 15.8+)% with duration ≥6 months*62%40%ITT population (final analysis)
Overall Survival
Final Analysis (median duration of follow-up of 14.3 months after 365 patient events)OSKEYTRUDA® + Carboplatin+ Paclitaxel/Nab-PaclitaxelPlacebo + Carboplatin+ Paclitaxel/Nab-Paclitaxel168197HR=0.71 [95% CI: 0.58, 0.88]Kaplan-Meier Curve for Overall Survival in the KEYNOTE-407 trial intent-to-treat population (final analysis)
AE=adverse management; AUC= area under the concentration; BICR=blinded independent central review; carb pac/nab-pac= carboplatin + paclitaxel or + nab-paclitaxel; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; mDOR= median duration of response; mOS= median overall survival; NA=not available; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PD-L1= programmed death ligand 1; PFS= progression-free survival; RECIST=response evaluation criteria in solid tumours; TPS=tumor proportion score
¶Based on the stratified Cox proportional hazard model
*Based on Kaplan-Meier estimation
a ‘+’ indicates there is no progressive disease by the time of last disease assessment
b At the initial interim analysis (n=101 for KEYTRUDA® combination therapy, n=102 for placebo), a statistically significant difference was observed; ORR was 58% [95% CI (48, 68)] and 35% [95% CI (26, 45)] for placebo, p=0.0004KEYTRUDA® demonstrated safety profile in squamous metastatic NSCLC in the KEYNOTE-407 trial
The most common Grade 3–5 treatment-related adverse events for patients treated with KEYTRUDA® were:
KEYTRUDA® + plat/pac (n=278)
%Placebo + plat/pac (n=280)
%Neutropenia21.2%22.5%Anemia13.7%15.4%Thrombocytopenia6.5%5.7%Neutrophil count decreased6.1%8.6%Febrile neutropenia5.0%3.6%- Treatment was discontinued for treatment-related adverse events in 9.0% of the 278 patients receiving KEYTRUDA®, carboplatin and either paclitaxel or nab-paclitaxel and in 3.2% of the 280 patients receiving placebo, carboplatin and either paclitaxel or nab-paclitaxel
- The most common treatment-related adverse events leading to study discontinuation (occurring in more than 3 patients) were pneumonitis (n=4) and sepsis (n=3)
- The median time to discontinuation for treatment-related adverse events was 1.9 months.
Treatment-related adverse events, any grade (reported in ≥20% of patients) were:
KEYTRUDA® + Carboplatin + Paclitaxel or Nab-Paclitaxel (n=278)
%Placebo + Carboplatin + Paclitaxel or Nab-Paclitaxel (n=280)
%Alopecia45.335.8Anemia44.241.8Neutropenia34.930.7Nausea30.625.4Thrombocytopenia29.120.7Diarrhea21.916.8For the complete list of treatment-related adverse events, please consult the Product Monograph
AE=adverse management; AUC= area under the concentration; BICR=blinded independent central review; carb pac/nab-pac= carboplatin + paclitaxel or + nab-paclitaxel; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; mDOR= median duration of response; mOS= median overall survival; NA=not available; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PD-L1= programmed death ligand 1; PFS= progression-free survival; RECIST=response evaluation criteria in solid tumours; TPS=tumor proportion score
¶Based on the stratified Cox proportional hazard model
*Based on Kaplan-Meier estimation
a ‘+’ indicates there is no progressive disease by the time of last disease assessment
b At the initial interim analysis (n=101 for KEYTRUDA® combination therapy, n=102 for placebo), a statistically significant difference was observed; ORR was 58% [95% CI (48, 68)] and 35% [95% CI (26, 45)] for placebo, p=0.0004
KEYTRUDA® in the second-line setting for metastatic non-small cell lung cancer (NSCLC)1
-
EXPLORE KEYTRUDA® in the KEYNOTE-010 trial for patients with metastatic NSCLC previously treated with chemotherapy
KEYNOTE-010 trial: Controlled, open-label trial in metastatic NSCLC patients previously treated with chemotherapy
Trial overview
- Multicenter, randomized, open-label trial encompassing 1,033 patients
- Key eligibility criteria:
- Metastatic NSCLC that had progressed following platinum-containing chemotherapy (and if appropriate, targeted therapy for ALK or EGFR mutations)
- PD-L1 TPS ≥1%
Treatment arms
KEYTRUDA® 2 mg/kg
KEYTRUDA® 10mg/kg
Doxetacel 75 mg/m2 Q3W
KEYTRUDA® 2 mg/kg, KEYTRUDA® 10mg/kg are not recommended doses.
Primary endpoints
- Overall survival
- Progression-free survival, as assessed by BICR using RECIST 1.1, in the subgroup of patients with TPS ≥50% and the overall population with TPS ≥1%
Secondary endpoints
- Objective response rate, in the subgroup of patients with TPS ≥50% and the overall population with TPS ≥1%
AE=adverse management; BICR=blinded independent central review; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; NA=not available; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PD-L1= programmed death ligand 1; PFS= progression-free survival; Q3W= every 3 weeks; RECIST=response evaluation criteria in solid tumours; TPS=tumor proportion score.
* Based on the stratified Cox proportional hazard model
**The confidence levels correspond to the allocated Type I error of 0.00825 and 0.001 for the OS and PFS endpoints, respectively.
† Based on stratified log-rank test
‡ Based on patients with a best overall response as confirmed complete or partial response
¶ Based on Kaplan-Meier estimation
c Statistically significant based on a pre-specified α level of 0.00825 for the two pairwise comparisons versus docetaxel using a Hochberg procedure
d All responses were partial responsesITT population
Overall Survival (primary endpoint)
Overall survivalKEYTRUDA®
2 mg/kg Q3W (n=344)KEYTRUDA®
10 mg/kg Q3W (n=346)Docetaxel 75 mg/m2 Q3W (n=343)50%
(HR** 0.71 [98.35% CI: 0.55, 0.92]; p<0.001†c)45%
(HR** 0.61 [98.35% CI: 0.47, 0.79]; p<0.001†c)56%
(98.35% CI)KEYTRUDA® 2 mg/kg, KEYTRUDA® 10mg/kg are not recommended doses.
Kaplan-Meier Curve for Overall Survival in the KEYNOTE-010 trial (TPS ≥ 1%, intent to treat population)
Median overall survivalKEYTRUDA®
2 mg/kg
KEYTRUDA®
10 mg/kgDocetaxel 75 mg/m210.4 months
(95% CI: 9.4, 11.9)12.7 months
(95% CI: 10.0, 17.3)8.5 months
(95% CI: 7.5, 9.8)Progression Free Survival (primary endpoint)
Progression-free survivalKEYTRUDA®
2 mg/kg Q3WKEYTRUDA®
10 mg/kg Q3WDocetaxel 75 mg/m2 Q3W77% patients with event
HR=0.88 (0.66, 1.15) p=0.068 vs Docetaxel 75 mg/m274% patients with event
HR=0.79 (0.60, 1.05) p=0.005 vs Docetaxel 75 mg/m275% patients with event
(98.35% CI)KEYTRUDA® 2 mg/kg, KEYTRUDA® 10mg/kg are not recommended doses.
Median Progression-Free SurvivalKEYTRUDA®
2 mg/kgKEYTRUDA®
10 mg/kgDocetaxel 75 mg/m23.9 months
(95% CI: 9.4, 11.9)4.0 months
(95% CI: 10.0, 17.3)4.0 months
(95% CI: 7.5, 9.8)KEYTRUDA® 2 mg/kg, KEYTRUDA® 10mg/kg are not recommended doses.
Objective Response Rate (secondary endpoint)
Objective Response RateKEYTRUDA®
2 mg/kgKEYTRUDA®
10 mg/kgDocetaxel 75 mg/m218%
(95% CI: 14, 23)18%
(95% CI:5, 23)9%
(95% CI: 7, 13)KEYTRUDA® 2 mg/kg, KEYTRUDA® 10mg/kg are not recommended doses.
AE=adverse management; BICR=blinded independent central review; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; NA=not available; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PD-L1= programmed death ligand 1; PFS= progression-free survival; Q3W= every 3 weeks; RECIST=response evaluation criteria in solid tumours; TPS=tumor proportion score.
* Based on the stratified Cox proportional hazard model
**The confidence levels correspond to the allocated Type I error of 0.00825 and 0.001 for the OS and PFS endpoints, respectively.
† Based on stratified log-rank test
‡ Based on patients with a best overall response as confirmed complete or partial response
¶ Based on Kaplan-Meier estimation
c Statistically significant based on a pre-specified α level of 0.00825 for the two pairwise comparisons versus docetaxel using a Hochberg procedure
d All responses were partial responsesKEYTRUDA® safety profile results in the treatment of metastatic NSCLC in the second-line setting in the KEYNOTE-010 trial
The most common grades 3 to 5 treatment-related adverse events, (reported in ≥ 1% of patients of either KEYTRUDA® or Docetaxel) were (pooled analysis):
Adverse ReactionKEYTRUDA® 2 or 10 mg/kg Q3W
(n=682)
%Docetaxel 75 mg/kg2 Q3W
(n=309)
%Pneumonitis1.80.3Fatigue1.53.6- The median time to discontinuation for treatment-related adverse events was 2.5 months.
- Treatment was discontinued for treatment-related adverse events in 5.0% of patients receiving KEYTRUDA®.
- The most common treatment-related adverse events leading to permanent discontinuation was pneumonitis (1.8%, n=12)
Treatment-related adverse events, any grade (reported in ≥ 10% of patients of either KEYTRUDA® or Docetaxel) were (pooled analysis):
Adverse ReactionKEYTRUDA® 2 or 10 mg/kg Q3W
(n=682)
%Docetaxel 75 mg/kg2 Q3W
(n=309)
%Fatigue13.924.9Decreased appetite11.615.9Rash10.74.5Nausea10.014.6Diarrhea6.718.1Asthenia5.711.3Anemia3.512.9Stomatitis2.913.9For the complete list of treatment-related adverse events, please consult the Product Monograph
AE=adverse management; BICR=blinded independent central review; CI= confidence interval; HR=hazard ratio; ITT= intent-to-treat; NA=not available; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS= overall survival; PD-L1= programmed death ligand 1; PFS= progression-free survival; Q3W= every 3 weeks; RECIST=response evaluation criteria in solid tumours; TPS=tumor proportion score.
* Based on the stratified Cox proportional hazard model
**The confidence levels correspond to the allocated Type I error of 0.00825 and 0.001 for the OS and PFS endpoints, respectively.
† Based on stratified log-rank test
‡ Based on patients with a best overall response as confirmed complete or partial response
¶ Based on Kaplan-Meier estimation
c Statistically significant based on a pre-specified α level of 0.00825 for the two pairwise comparisons versus docetaxel using a Hochberg procedure
d All responses were partial responses
References:
1. Merck Canada Inc. KEYTRUDA® Product Monograph. April 19, 2023.
2. ASCO and OH (CCO) Joint Guideline Update. Available at: https://www.cancercareontario.ca/en/guidelines-advice/types-of-cancer/62681
3. Hanna, N et al. (2020). Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO and OH (CCO) Joint Guideline Update. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 38(14), 1608–1632. https://doi.org/10.1200/JCO.19.03022
4. Rastogi M, et al. (2016). An unusual response with long term survival using erlotinib in NSCLC lung with brain metastases. BMJ Case Rep. bcr2015213239. https://doi.org/10.1136/bcr-2015-213239
5. Medline. Available at: https://medlineplus.gov/ency/imagepages/1183.htm
6. Dromain C, Beigelman C, Pozzessere C, Duran R, Digklia A. Imaging of tumour response to immunotherapy. Eur Radiol Exp. 2020 Jan 3;4(1):2.
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