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Clinical Trial
. 2024 Dec;29(12):1825-1839.
doi: 10.1007/s10147-024-02632-x. Epub 2024 Oct 9.

First-line pembrolizumab with or without chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up of the Japanese population of KEYNOTE‑048

Nobuhiko Oridate  1 , Shunji Takahashi  2 , Kaoru Tanaka  3 , Yasushi Shimizu  4 , Yasushi Fujimoto  5 , Koji Matsumoto  6 , Tomoya Yokota  7 , Tomoko Yamazaki  8 , Masanobu Takahashi  9 , Tsutomu Ueda  10 , Nobuhiro Hanai  11 , Hironori Yamaguchi  12 , Hiroki Hara  13 , Tomokazu Yoshizaki  14 , Ryuji Yasumatsu  15 , Masahiro Nakayama  16 , Kiyoto Shiga  17 , Takashi Fujii  18 , Kenji Mitsugi  19 , Kenichi Takahashi  20 , Nijiro Nohata  20 , Burak Gumuscu  21 , Nati Lerman  21 , Makoto Tahara  22
Affiliations
Clinical Trial

First-line pembrolizumab with or without chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up of the Japanese population of KEYNOTE‑048

Nobuhiko Oridate et al. Int J Clin Oncol. 2024 Dec.

Abstract

Background: Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up.

Methods: Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations.

Results: In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2-81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13-1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34-1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27-1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27-2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56-2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57-2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively.

Conclusion: After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC.

Clinical trial registration: NCT02358031.

Keywords: EXTREME; Immunotherapy; PD-L1; Pembrolizumab; Recurrent/metastatic head and neck squamous cell carcinoma.

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Conflict of interest statement

Declarations. Conflict of interest: Nobuhiko Oridate has received honoraria from MSD, Ono Pharmaceutical, Bristol Myers Squibb Japan, Merck Biopharm Japan, and Taiho Pharmaceutical. Shunji Takahashi has received honoraria from MSD, Eisai, and Ono Pharmaceutical and grants from Taiho Pharmaceutical, Daiichi Sankyo, Novartis, Ono Pharmaceutical, Eisai, BMS, Bayer, and Astra Zeneca. Kaoru Tanaka has received personal fees from Astra Zeneca, Merck Biopharma, Eisai, Bristol Myers Squibb, Ono Pharmaceutical, MSD, Kyowa Kirin, Chugai Pharmaceutical, Takeda Pharmaceutical, Taiho Pharmaceutical, and Novartis Pharma, outside the submitted work. Yasushi Shimizu has received research funding from MSD. Koji Matsumoto has received honoraria from MSD, Kyowa Kirin, Daiichi Sankyo, Eli Lilly, and Chugai Pharmaceutical Co. and received trial fee from Daiichi Sankyo, MSD, Eli Lilly, Gildea Sciences, and Eisai. Tomoya Yokota has received research funding from MSD. Masanobu Takahashi has received lecture fees from Daiichi Sankyo, Ono Pharmaceuticals, Bristol Myers Squibb, Taiho Pharmaceutical Co. and research funding from Ono Pharmaceutical, Chugai Pharmaceutical, and MSD, outside the submitted work. Tsutomu Ueda has received research funding from Lilly and personal fees from Rakuten Medical, Merck Biopharma, Mitsubishi Tanabe Pharma, MSD, and Bristol Myers Squibb. Nobuhiro Hanai has received honoraria from Rakuten Medical K.K. and research funding from MSD K.K. and Adlai Nortye USA Inc. Hiroki Hara has received honoraria from Bristol Myers Squibb, Chugai, Daiichi Sankyo, Lilly, Merck Biopharma, Miyarisan, MSD, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, and Yakult Honsha and research funding from ALX oncology, Amgen, Astellas, Astra Zeneca, Bayer, BioGene, Chugai, Daiichi Sankyo, Janssen, Jazz Pharma, MSD, Ono Pharmaceutical, and Taiho Pharmaceutical. Kenichi Takahashi is an employee of MSD K.K., Tokyo, Japan and owns stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Nijiro Nohata is an employee of MSD K.K., Tokyo, Japan and owns stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Burak Gumuscu is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Nati Lerman is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Makoto Tahara has received honoraria from Eisai, MSD, Merck Biopharma, Lilly and research funding from Bayer, Astra Zeneca, Ono Pharmaceutical, and Pfizer. Yasushi Fujimoto, Tomoko Yamazaki, Hironori Yamaguchi, Tomokazu Yoshizaki Ryuji Yasumatsu, Masahiro Nakayama, Kiyoto Shiga, Takashi Fujii, and Kenji Mitsugi declare they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Pembrolizumab versus EXTREME in the A PD-L1 CPS ≥ 20, B PD-L1 CPS ≥ 1, and C total Japanese populations at long-term follow-up and pembrolizumab-chemotherapy versus EXTREME in the D PD-L1 CPS ≥ 20, E PD-L1 CPS ≥ 1, and F total Japanese populations. aFrom the product-limit (Kaplan–Meier) method for censored data. bOn the basis of a Cox proportional hazards regression model with the Efron method of tie handling with treatment as a covariate. CI confidence interval, CPS combined positive score, HR hazard ratio, OS overall survival, PD-L1 programmed cell death ligand 1
Fig. 1
Fig. 1
Pembrolizumab versus EXTREME in the A PD-L1 CPS ≥ 20, B PD-L1 CPS ≥ 1, and C total Japanese populations at long-term follow-up and pembrolizumab-chemotherapy versus EXTREME in the D PD-L1 CPS ≥ 20, E PD-L1 CPS ≥ 1, and F total Japanese populations. aFrom the product-limit (Kaplan–Meier) method for censored data. bOn the basis of a Cox proportional hazards regression model with the Efron method of tie handling with treatment as a covariate. CI confidence interval, CPS combined positive score, HR hazard ratio, OS overall survival, PD-L1 programmed cell death ligand 1
Fig. 1
Fig. 1
Pembrolizumab versus EXTREME in the A PD-L1 CPS ≥ 20, B PD-L1 CPS ≥ 1, and C total Japanese populations at long-term follow-up and pembrolizumab-chemotherapy versus EXTREME in the D PD-L1 CPS ≥ 20, E PD-L1 CPS ≥ 1, and F total Japanese populations. aFrom the product-limit (Kaplan–Meier) method for censored data. bOn the basis of a Cox proportional hazards regression model with the Efron method of tie handling with treatment as a covariate. CI confidence interval, CPS combined positive score, HR hazard ratio, OS overall survival, PD-L1 programmed cell death ligand 1
Fig. 2
Fig. 2
Pembrolizumab versus EXTREME in the A PD-L1 CPS ≥ 20, B PD-L1 CPS ≥ 1, and C total Japanese populations at long-term follow-up and pembrolizumab-chemotherapy versus EXTREME in the D PD-L1 CPS ≥ 20, E PD-L1 CPS ≥ 1, and F total Japanese populations. aFrom the product-limit (Kaplan–Meier) method for censored data. bOn the basis of a Cox proportional hazards regression model with the Efron’s method of tie handling with treatment as a covariate. CI confidence interval, CPS combined positive score, HR hazard ratio, PD-L1 programmed cell death ligand 1, PFS progression-free survival
Fig. 2
Fig. 2
Pembrolizumab versus EXTREME in the A PD-L1 CPS ≥ 20, B PD-L1 CPS ≥ 1, and C total Japanese populations at long-term follow-up and pembrolizumab-chemotherapy versus EXTREME in the D PD-L1 CPS ≥ 20, E PD-L1 CPS ≥ 1, and F total Japanese populations. aFrom the product-limit (Kaplan–Meier) method for censored data. bOn the basis of a Cox proportional hazards regression model with the Efron’s method of tie handling with treatment as a covariate. CI confidence interval, CPS combined positive score, HR hazard ratio, PD-L1 programmed cell death ligand 1, PFS progression-free survival
Fig. 2
Fig. 2
Pembrolizumab versus EXTREME in the A PD-L1 CPS ≥ 20, B PD-L1 CPS ≥ 1, and C total Japanese populations at long-term follow-up and pembrolizumab-chemotherapy versus EXTREME in the D PD-L1 CPS ≥ 20, E PD-L1 CPS ≥ 1, and F total Japanese populations. aFrom the product-limit (Kaplan–Meier) method for censored data. bOn the basis of a Cox proportional hazards regression model with the Efron’s method of tie handling with treatment as a covariate. CI confidence interval, CPS combined positive score, HR hazard ratio, PD-L1 programmed cell death ligand 1, PFS progression-free survival
Fig. 3
Fig. 3
Time to response and response duration at long-term follow-up in the total Japanese population receiving A pembrolizumab, B pembrolizumab-chemotherapy, and C EXTREME
Fig. 3
Fig. 3
Time to response and response duration at long-term follow-up in the total Japanese population receiving A pembrolizumab, B pembrolizumab-chemotherapy, and C EXTREME
Fig. 4
Fig. 4
Change from baseline in target lesion size at long-term follow-up in the total Japanese population receiving A pembrolizumab monotherapy, B pembrolizumab-chemotherapy, and C EXTREME
Fig. 4
Fig. 4
Change from baseline in target lesion size at long-term follow-up in the total Japanese population receiving A pembrolizumab monotherapy, B pembrolizumab-chemotherapy, and C EXTREME
See this image and copyright information in PMC

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