Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: Opdated results of the phase III keynote-048 study

• Main Authors: Harrington, Kevin J., Burtness, Barbara, Greil, Richard, Soulieres, Denis, Tahara, Makoto, de Castro Jr, Gilberto, Psyrri, Amanda, Brana, Irene, Baste, Neus, Neupane, Prakash, Bratland, Ase, Fuereder, Thorsten, Hughes, Brett G. M., Mesia, Ricard, Ngamphaiboon, Nuttapong, Rordorf, Tamara, Wan Ishak, Wan Zamaniah, Lin, Jianxin, Gumuscu, Burak, Swaby, Ramona F., Rischin, Danny
• Format: Article
• Published: Lippincott Williams & Wilkins 2023
• Subjects: R Medicine (General); RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Online Access: http://eprints.um.edu.my/38695/

PURPOSEPembrolizumab 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.METHODSPatients 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.RESULTSThe 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.CONCLUSIONWith 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.