KEYTRUDA® in the first-line setting for metastatic or unresectable head and neck cancer (HNSCC)1
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EXPLORE KEYTRUDA® IN THE KEYNOTE-048 TRIAL for patients with unresectable recurrent or metastatic HNSCC
KEYNOTE-048 trial: Phase III trial of KEYTRUDA® in patients with metastatic or recurrent HNSCC who had not previously received systemic therapy for recurrent or metastatic disease and who were considered incurable by local therapies
Trial overview
- Randomized, multicenter, open-label, active-controlled trial
- Treatment arms were KEYTRUDA® monotherapy, KEYTRUDA® + carboplatin AUC and FU or KEYTRUDA®+ cisplatin and FU; and cetuximab + carboplatin AUC and FU or + cetuximab + cisplatin and FU
- Encompassed 882 patients with metastatic or recurrent HNSCC who had not previously received systemic therapy
Primary endpoints
- Overall survival
- Progression-free survival (assessed by BICR using RECIST 1.1)
Secondary endpoint
- Objective response rate (assessed by BICR using RECIST 1.1)
AE=adverse event; ALT=alanine aminotransferase; AST=aspartate aminotransferase; AUC=area under the curve; CI=confidence interval; ECOG PS=Eastern Cooperative Oncology Group Performance Status; FU=fluorouracil; HNCC=head and neck squamous cell carcinoma; HPV=human papillomavirus; OS=overall survival; PD-L1=programmed death-ligand 1; PFS=progression-free survival; RECIST=response evaluation criteria in solid tumours.
† Based on the stratified Cox proportional hazard model
‡ Based on stratified log-rank test
#Cetuximab, platinum, and FUKEYTRUDA® Monotherapy
Overall survival
KEYNOTE-048 trial demonstrated a statistically significant improvement in OS in patients whose tumors expressed PD-L1 CPS≥1 randomized to pembrolizumab monotherapy compared to standard treatment#
26% reduction in the instantaneous risk of death with KEYTRUDA® Monotherapy [197/257 with event] vs. Standard Treatment [229/255 with event]# (HR=0.74 [95% CI: 0.61, 0.90]; p=0.00133‡)
Kaplan-Meier Curve for Overall Survival in the KEYNOTE-048 trial for KEYTRUDA® monotherapy with CPS≥1 at final analysis
mOSStandard Treatment
(n= 255)KEYTRUDA® Monotherapy
(n=257)10.3 months
(95% CI: 9.0, 11.5)12.3 months
(95% CI: 10.8, 14.3)Progression-free survival
KEYTRUDA® monotherapy vs. cetuximab + platinum chemotherapy and FU in patients with metastatic or recurrent HNSCC who had not previously received systemic therapy for recurrent or metastatic disease and who were considered incurable by local therapies in the KEYNOTE-048 trial1
The co-primary endpoint PFS did not reach statistical significance.
PFS was not statistically significant at the final analysis (HR=1.13† [95% CI: 0.94, 1.36; p=0.8958‡]).
Number of patients with event:
- 89% (228/257) KEYTRUDA® monotherapy
- 93% (237/255) cetuximab + platinum and FU
Treatment ArmsKEYTRUDA® MonotherapyCetuximab + platinum chemotherapy and FUPFS3.2 months (95% CI: 2.2, 3.4)5 months (95% CI: 4.8, 6.0)Hazard RatioHR=1.13†
[95% CI: 0.94, 1.36 p=0.8958‡]KEYTRUDA® in Combination
Overall survival
KEYNOTE-048 trial demonstrated a statistically significant improvement in OS for patients randomized to KEYTRUDA® in combination with chemotherapy compared to standard treatment#
28% reduction in the instantaneous risk of death with KEYTRUDA® plus chemotherapy [213/281with event] vs. Standard Treatment [247/278 with event]# (HR=0.72† [95% CI: 0.60, 0.87; p=0.00025‡])
Kaplan-Meier Curve for Overall Survival in the KEYNOTE-048 trial for KEYTRUDA® plus chemotherapy at Final Analysis
mOSStandard Treatment
(n=278)KEYTRUDA®+ platinum chemotherapy
(n=281)10.7 months
(95% CI: 9.3, 11.7)13 months
(95% CI: 10.9, 14.7)Progression-free survival
KEYTRUDA® + platinum chemotherapy and FU vs. cetuximab + platinum chemotherapy and FU in patients with metastatic or recurrent HNSCC who had not previously received systemic therapy for recurrent or metastatic disease and who were considered incurable by local therapies in the KEYNOTE-048 trial1
The co-primary endpoint PFS did not reach statistical significance.
PFS was not statistically significant at the final analysis (HR=0.93† [95% CI: 0.78, 1.11; p=0.2121‡]).
Number of patients with event:
- 89% (250/281) KEYTRUDA® + platinum chemotherapy and FU
- 94% (260/278) cetuximab + platinum and FU
Treatment ArmsKEYTRUDA® + platinum chemotherapy and FUCetuximab + platinum chemotherapy and FUPFS4.9 months (95% CI: 4.7, 6.1)5.2 months (95% CI: 4.9, 6.1)Hazard RatioHR=0.93†
[95% CI: 0.78, 1.11 p=0.2121‡]Median duration of response
KEYTRUDA® monotherapy:
20.9 months (range 1.5+, 34.8+)Cetuximab + platinum chemotherapy and FU:
4.5 months (range 1.2+, 30.6+)KEYTRUDA®
+ platinum chemotherapy and FU:
6.7 months (range 1.6+, 30.4+)Cetuximab
+ platinum chemotherapy and FU:
4.3 months (range 1.2+, 27.9+)AE=adverse event; ALT=alanine aminotransferase; AST=aspartate aminotransferase; AUC=area under the curve; CI=confidence interval; ECOG PS=Eastern Cooperative Oncology Group Performance Status; FU=fluorouracil; HNCC=head and neck squamous cell carcinoma; HPV=human papillomavirus; OS=overall survival; PD-L1=programmed death-ligand 1; PFS=progression-free survival; RECIST=response evaluation criteria in solid tumours.
† Based on the stratified Cox proportional hazard model
‡ Based on stratified log-rank test
#Cetuximab, platinum, and FUKEYTRUDA® demonstrated safety profile in the first-line setting for recurrent or metastatic HNSCC
The most common Grades 3-5 treatment-related adverse events reported in KEYTRUDA® monotherapy and KEYTRUDA® combination therapy were:
Adverse reactionKEYTRUDA® monotherapy
(n=300) %Hyponatremia2Pneumonitis1.3Fatigue1Adverse reactionKEYTRUDA® + platinum chemotherapy and FU
(n=276) %Anemia19.6Neutropenia17.8Neutrophil count decreased9.8Mucosal inflammation9.4Thrombocytopenia8.7Febrile neutropenia8.0Stomatitis8.0Fatigue6.9Nausea5.4White blood cell decreased5.4Platelet count decreased5.1Treatment-related adverse events, any grades (reported in ≥10% of patients) were:a
Adverse reactionKEYTRUDA® monotherapy (n=300) %KEYTRUDA® + platinum chemotherapy and FU (n=276) %Cetuximab + platinum chemotherapy and FU (n=287) %Fatigue14.330.428.9Hypothyroidism13.013.00.3Diarrhea5.718.126.5Decreased appetite5.322.521.6Anemia4.048.641.1Constipation3.010.110.8Asthenia2.311.610.5Vomiting2.327.222.3Thrombocytopenia1.327.221.6Hypomagnesemia1.010.533.1Neutropenia1.033.031.0Leukopenia0.712.313.2Stomatitis0.725.024.4Blood creatinine increased0.711.25.6White blood cell count decreased0.713.015.0Neutrophil count decreased0.316.318.8Platelet count decreased0.318.516.0
aAll patients as treated population.- Treatment discontinuation due to treatment-related adverse events was 5.0% for KEYTRUDA® monotherapy (n=300) and 25.0% for KEYTRUDA® + platinum chemotherapy and FU (n=276).
- The median time to discontinuation for treatment-related adverse events was 7.0 months for patients treated with KEYTRUDA® as monotherapy and 0.2 months for patients treated with KEYTRUDA® in combination with chemotherapy.
For the complete list of treatment-related adverse events, please consult the Product Monograph.
AE=adverse event; ALT=alanine aminotransferase; AST=aspartate aminotransferase; AUC=area under the curve; CI=confidence interval; ECOG PS=Eastern Cooperative Oncology Group Performance Status; FU=fluorouracil; HNCC=head and neck squamous cell carcinoma; HPV=human papillomavirus; OS=overall survival; PD-L1=programmed death-ligand 1; PFS=progression-free survival; RECIST=response evaluation criteria in solid tumours.
† Based on the stratified Cox proportional hazard model
‡ Based on stratified log-rank test
#Cetuximab, platinum, and FU
References:
1. Merck Canada Inc. KEYTRUDA® Product Monograph. April 19, 2023.
2. National Comprehensive Cancer Network®. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Head and Neck Cancers, version 2. 2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
CA-OHN-00038