First-line Pembrolizumab ± chemotherapy for Recurrent/metastatic Head and Neck Cancer: Japanese Subgroup of KEYNOTE-048

Overview

Journal Int J Clin Oncol

Specialty Oncology

Date 2022 Oct 20

PMID 36264378

Authors

Shunji Takahashi

Nobuhiko Oridate

Kaoru Tanaka

Yasushi Shimizu

Yasushi Fujimoto

Koji Matsumoto

Tomoya Yokota

Tomoko Yamazaki

Masanobu Takahashi

Tsutomu Ueda

Nobuhiro Hanai

Hironori Yamaguchi

Hiroki Hara

Tomokazu Yoshizaki

Ryuji Yasumatsu

Masahiro Nakayama

Kiyoto Shiga

Takashi Fujii

Kenji Mitsugi

Kenichi Takahashi

Nijiro Nohata

Burak Gumuscu

Ramona F Swaby

Makato Tahara

Affiliations

Soon will be listed here.

Abstract

Background: Here, we report the results of the Japanese subgroup of the phase 3 KEYNOTE-048 study of pembrolizumab alone, pembrolizumab plus platinum and 5-fluorouracil (pembrolizumab-chemotherapy), or cetuximab plus platinum and 5-fluorouracil (EXTREME) in previously untreated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Methods: Primary end points were overall survival (OS) and progression-free survival (PFS). Efficacy was evaluated in patients with PD-L1 combined positive score (CPS) ≥ 20 and ≥ 1 and the total Japanese subgroup (n = 67).

Results: At data cutoff (25 February 2019), pembrolizumab led to longer OS versus EXTREME in the PD-L1 CPS ≥ 20 subgroup (median, 28.2 vs. 13.3 months; HR, 0.29 [95% CI 0.09-0.89]) and to similar OS in the total Japanese (23.4 vs. 13.6 months; HR, 0.51 [95% CI 0.25-1.05]) and CPS ≥ 1 subgroups (22.6 vs. 15.8 months; HR, 0.66 [95% CI 0.31-1.41]). Pembrolizumab-chemotherapy led to similar OS versus EXTREME in the PD-L1 CPS ≥ 20 (median, 18.1 vs. 15.8 months; HR, 0.72 [95% CI 0.23-2.19]), CPS ≥ 1 (12.6 vs. 15.8 months; HR, 1.19 [95% CI 0.55-2.58]), and total Japanese subgroups (12.6 vs. 13.3 months; unadjusted HR, 1.10 [95% CI 0.55-2.22]). Median PFS was similar for pembrolizumab and pembrolizumab-chemotherapy versus EXTREME in all subgroups. Grades 3-5 treatment-related adverse events occurred in 5 (22%), 19 (76%), and 17 (89%) patients receiving pembrolizumab, pembrolizumab-chemotherapy, and EXTREME, respectively. One patient receiving pembrolizumab-chemotherapy died because of treatment-related pneumonitis.

Conclusion: These results support the use of first-line pembrolizumab and pembrolizumab-chemotherapy for Japanese patients with R/M HNSCC. Clinical trial registry ClinicalTrials.gov, NCT02358031.

Citing Articles

Real-World Evidence on the Effectiveness of Pembrolizumab in Patients With Recurrent/Metastatic/Unresectable Head and Neck Squamous Cell Cancer: A Systematic Review and Meta-Analysis.

Meenu M, Dhiman P, Kumar M, Pradhan P, Pandey S Cureus. 2025; 17(1):e76709.

PMID: 39748883 PMC: 11694497. DOI: 10.7759/cureus.76709.

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.

Oridate N, Takahashi S, Tanaka K, Shimizu Y, Fujimoto Y, Matsumoto K Int J Clin Oncol. 2024; 29(12):1825-1839.

PMID: 39382718 PMC: 11588814. DOI: 10.1007/s10147-024-02632-x.

Standardized Digital Image Analysis of PD-L1 Expression in Head and Neck Squamous Cell Carcinoma Reveals Intra- and Inter-Sample Heterogeneity with Therapeutic Implications.

Deuss E, Kurten C, Fehr L, Kahl L, Zimmer S, Kunzel J Cancers (Basel). 2024; 16(11).

PMID: 38893222 PMC: 11171694. DOI: 10.3390/cancers16112103.

Penpulimab combined with anlotinib in patients with R/M HNSCC after failure of platinum-based chemotherapy: a single-arm, multicenter, phase Ⅱ study.

Shi Y, Gao L, Tian Y, Bai C, Chen J, Wang J ESMO Open. 2023; 8(6):102194.

PMID: 38100934 PMC: 10774955. DOI: 10.1016/j.esmoop.2023.102194.

Gold Nanoparticles Enhance the Tumor Growth-Suppressing Effects of Cetuximab and Radiotherapy in Head and Neck Cancer In Vitro and In Vivo.

Sato T, Kakei Y, Hasegawa T, Kashin M, Teraoka S, Yamaguchi A Cancers (Basel). 2023; 15(23).

PMID: 38067400 PMC: 10705767. DOI: 10.3390/cancers15235697.

References

Ferris R, Blumenschein Jr G, Fayette J, Guigay J, Colevas A, Licitra L . Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016; 375(19):1856-1867. PMC: 5564292. DOI: 10.1056/NEJMoa1602252. View

Chow L . Head and Neck Cancer. N Engl J Med. 2020; 382(1):60-72. DOI: 10.1056/NEJMra1715715. View

Kiyota N, Hasegawa Y, Takahashi S, Yokota T, Yen C, Iwae S . A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator's choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141. Oral Oncol. 2017; 73:138-146. DOI: 10.1016/j.oraloncology.2017.07.023. View

Vermorken J, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S . Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008; 359(11):1116-27. DOI: 10.1056/NEJMoa0802656. View

Yoshino T, Hasegawa Y, Takahashi S, Monden N, Homma A, Okami K . Platinum-based chemotherapy plus cetuximab for the first-line treatment of Japanese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: results of a phase II trial. Jpn J Clin Oncol. 2013; 43(5):524-31. PMC: 3638634. DOI: 10.1093/jjco/hyt034. View

Burtness B, Harrington K, Greil R, Soulieres D, Tahara M, de Castro Jr G . Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019; 394(10212):1915-1928. DOI: 10.1016/S0140-6736(19)32591-7. View

Gupta B, Johnson N, Kumar N . Global Epidemiology of Head and Neck Cancers: A Continuing Challenge. Oncology. 2016; 91(1):13-23. DOI: 10.1159/000446117. View

Pons-Tostivint E, Latouche A, Vaflard P, Ricci F, Loirat D, Hescot S . Comparative Analysis of Durable Responses on Immune Checkpoint Inhibitors Versus Other Systemic Therapies: A Pooled Analysis of Phase III Trials. JCO Precis Oncol. 2022; 3:1-10. DOI: 10.1200/PO.18.00114. View

Cohen E, Soulieres D, Le Tourneau C, Dinis J, Licitra L, Ahn M . Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2018; 393(10167):156-167. DOI: 10.1016/S0140-6736(18)31999-8. View

10.

Tahara M, Muro K, Hasegawa Y, Chung H, Lin C, Keam B . Pembrolizumab in Asia-Pacific patients with advanced head and neck squamous cell carcinoma: Analyses from KEYNOTE-012. Cancer Sci. 2017; 109(3):771-776. PMC: 5834807. DOI: 10.1111/cas.13480. View

11.

Marur S, Forastiere A . Head and Neck Squamous Cell Carcinoma: Update on Epidemiology, Diagnosis, and Treatment. Mayo Clin Proc. 2016; 91(3):386-96. DOI: 10.1016/j.mayocp.2015.12.017. View

12.

Sano D, Fujisawa T, Tokuhisa M, Shimizu M, Sakagami T, Hatano T . Real-world Treatment Outcomes of the EXTREME Regimen as First-line Therapy for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: A Multi-center Retrospective Cohort Study in Japan. Anticancer Res. 2019; 39(12):6819-6827. DOI: 10.21873/anticanres.13898. View

13.

Hori R, Shinohara S, Kojima T, Kagoshima H, Kitamura M, Tateya I . Real-World Outcomes and Prognostic Factors in Patients Receiving Nivolumab Therapy for Recurrent or Metastatic Head and Neck Carcinoma. Cancers (Basel). 2019; 11(9). PMC: 6770631. DOI: 10.3390/cancers11091317. View

14.

Nibu K, Hayashi R, Asakage T, Ojiri H, Kimata Y, Kodaira T . Japanese Clinical Practice Guideline for Head and Neck Cancer. Auris Nasus Larynx. 2017; 44(4):375-380. DOI: 10.1016/j.anl.2017.02.004. View

15.

Pfister D, Spencer S, Adelstein D, Adkins D, Anzai Y, Brizel D . Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020; 18(7):873-898. DOI: 10.6004/jnccn.2020.0031. View