Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study
Kevin J Harrington, Barbara Burtness, Richard Greil, Denis Soulières, Makoto Tahara, Gilberto de Castro Jr, Amanda Psyrri, Irene Brana, Neus Basté, Prakash Neupane, Åse Bratland, Thorsten Fuereder, Brett G M Hughes, Ricard Mesia, Nuttapong Ngamphaiboon, Tamara Rordorf, Wan Zamaniah Wan Ishak, Jianxin Lin, Burak Gumuscu, Ramona F Swaby, Danny Rischin, Kevin J Harrington, Barbara Burtness, Richard Greil, Denis Soulières, Makoto Tahara, Gilberto de Castro Jr, Amanda Psyrri, Irene Brana, Neus Basté, Prakash Neupane, Åse Bratland, Thorsten Fuereder, Brett G M Hughes, Ricard Mesia, Nuttapong Ngamphaiboon, Tamara Rordorf, Wan Zamaniah Wan Ishak, Jianxin Lin, Burak Gumuscu, Ramona F Swaby, Danny Rischin
Abstract
Purpose: Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented.
Methods: Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Efficacy was evaluated in programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, CPS ≥ 1, and total populations, with no multiplicity or alpha adjustment.
Results: The median study follow-up was 45.0 months (interquartile range, 41.0-49.2; n = 882). At data cutoff (February 18, 2020), overall survival improved with pembrolizumab in the PD-L1 CPS ≥ 20 (hazard ratio [HR], 0.61; 95% CI, 0.46 to 0.81) and CPS ≥ 1 populations (HR, 0.74; 95% CI, 0.61 to 0.89) and was noninferior in the total population (HR, 0.81; 95% CI, 0.68 to 0.97). Overall survival improved with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.62; 95% CI, 0.46 to 0.84), CPS ≥ 1 (HR, 0.64; 95% CI, 0.53 to 0.78), and total (HR, 0.71; 95% CI, 0.59 to 0.85) populations. The objective response rate on second-course pembrolizumab was 27.3% (3 of 11). PFS2 improved with pembrolizumab in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.84) and CPS ≥ 1 (HR, 0.79; 95% CI, 0.66 to 0.95) populations and with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.86), CPS ≥ 1 (HR, 0.66; 95% CI, 0.55 to 0.81), and total (HR, 0.73; 95% CI, 0.61 to 0.88) populations. PFS2 was similar after pembrolizumab and longer after pembrolizumab-chemotherapy on next-line taxanes and shorter after pembrolizumab and similar after pembrolizumab-chemotherapy on next-line nontaxanes.
Conclusion: With a 4-year follow-up, first-line pembrolizumab and pembrolizumab-chemotherapy continued to demonstrate survival benefit versus cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Patients responded well to subsequent treatment after pembrolizumab-based therapy.
Trial registration: ClinicalTrials.gov NCT02358031.
Conflict of interest statement
Danny Rischin
This author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.
Research Funding: Genentech/Roche (Inst), Merck (Inst), Regeneron (Inst), Bristol Myers Squibb (Inst), GlaxoSmithKline (Inst), Sanofi (Inst), Kura Oncology (Inst), Merck KGaA (Inst)
No other potential conflicts of interest were reported.
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References
- Johnson DE, Burtness B, Leemans CR, et al. : Head and neck squamous cell carcinoma. Nat Rev Dis Primers 6:92, 2020
- Chow LQM: Head and neck cancer. N Engl J Med 382:60-72, 2020
- Burtness B, Harrington KJ, Greil R, et al. : 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 394:1915-1928, 2019
- Cohen EEW, Soulieres D, Le Tourneau C, et al. : 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 393:156-167, 2019
- Ferris RL, Blumenschein G, Jr, Fayette J, et al. : Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375:1856-1867, 2016
- Machiels JP, René Leemans C, Golusinski W, et al. : Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 31:1462-1475, 2020
- National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology. Head and Neck Cancers. Version.1 2021. Plymouth Meeting, PA, National Comprehensive Cancer Network, 2021
- Woodford RG, Zhou DD, Kok PS, et al. : The validity of progression-free survival 2 as a surrogate trial end point for overall survival. Cancer 128:1449-1457, 2022
- Ang KK, Harris J, Wheeler R, et al. : Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24-35, 2010
- Peterson LA, Bellile EL, Wolf GT, et al. : Cigarette use, comorbidities, and prognosis in a prospective head and neck squamous cell carcinoma population. Head Neck 38:1810-1820, 2016
- Haddad R, Concha-Benavente F, Blumenschein G, Jr, et al. : Nivolumab treatment beyond RECIST-defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: A subgroup analysis of a randomized phase 3 clinical trial. Cancer 125:3208-3218, 2019
- Le Tourneau C, Cohen EEW, Harrington KJ, et al. : Pembrolizumab for recurrent head and neck squamous cell carcinoma (HNSCC): Post hoc analyses of treatment options from the phase 3 KEYNOTE-040 trial. Ann Oncol 29 :viii373-viii374, 2018. (suppl 8)
- Saleh K, Daste A, Martin N, et al. : Response to salvage chemotherapy after progression on immune checkpoint inhibitors in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Eur J Cancer 121:123-129, 2019
- Kacew AJ, Harris EJ, Lorch JH, et al. : Chemotherapy after immune checkpoint blockade in patients with recurrent, metastatic squamous cell carcinoma of the head and neck. Oral Oncol 105:104676, 2020
- Kurosaki T, Mitani S, Tanaka K, et al. : Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: A single-center retrospective study. Anticancer Drugs 32:95-101, 2021
- Pestana RC, Becnel M, Rubin ML, et al. : Response rates and survival to systemic therapy after immune checkpoint inhibitor failure in recurrent/metastatic head and neck squamous cell carcinoma. Oral Oncol 101:104523, 2020
- Burtness B, Zhang Y, Harrington KJ, et al. : Further clinical interpretation and implications of KEYNOTE-048 findings—Authors' reply. Lancet 396:379-380, 2020
Source: PubMed