![]() ![]() 6 In the phase III KEYNOTE-040 study, patients with platinum-refractory R/M HNSCC (N = 495) were randomly assigned to pembrolizumab or standard-of-care systemic therapy. 023) and median overall survival (OS) was longer in patients with CPS ≥ 1 than CPS < 1 (10 v 5 months one-sided P =. 10, 11 In the phase Ib KEYNOTE-012 study of pembrolizumab monotherapy in R/M HNSCC (N = 192), objective response rate (ORR) was higher in patients with PD-L1 CPS ≥ 1 than CPS < 1 (21% v 6% one-sided P =. Pembrolizumab produces durable responses and robust antitumor activity in recurrent or metastatic (R/M) HNSCC, with greater benefit observed in PD-L1–enriched populations. The results indicate that although PD-L1 expression is useful, additional predictive biomarkers are needed for informing treatment decisions in low PD-L1–expressing recurrent or metastatic head and neck squamous cell carcinoma. These results support previous findings and demonstrate increased efficacy for pembrolizumab or pembrolizumab-chemotherapy with increasing PD-L1 expression. In the PD-L1 CPS < 1 subgroup, neither pembrolizumab nor pembrolizumab-chemotherapy demonstrated improvement in overall survival compared with cetuximab-chemotherapy. Pembrolizumab and pembrolizumab-chemotherapy demonstrated antitumor activity in the PD-L1 CPS 1-19 subgroup, with pembrolizumab-chemotherapy leading to numerically longer overall survival than cetuximab-chemotherapy. ![]() To further characterize the predictive value of PD-L1 expression, efficacy was analyzed in participants with PD-L1 CPS < 1 and CPS 1-19. Efficacy was assessed in participants with a programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 20 and CPS ≥ 1 and the total population. KEYNOTE-048 investigated pembrolizumab monotherapy and pembrolizumab plus chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma. Although expression of PD-L1 is common in HNSCC, some tumors have low or undetectable levels. 5- 7 PD-L1 expression in pembrolizumab trials is described by tumor proportion score (TPS), defined as the percentage of viable tumor cells showing partial or complete membrane PD-L1 staining, or combined positive score (CPS), defined as the number of PD-L1–positive tumor cells, lymphocytes, and macrophages divided by the total number of tumor cells, multiplied by 100. 3, 4 The anti–PD-1 antibodies pembrolizumab and nivolumab have demonstrated antitumor activity and acceptable safety in several cancers that overexpress PD-L1, including HNSCC. 2, 3 PD-1 is expressed on immune cells, including T cells, B cells, and activated monocytes, whereas PD-L1 is expressed by tumor cells, immune cells, and various nonhematopoietic cells. 1 PD-L1 overexpression activates the programmed death 1 (PD-1)/PD-L1 axis to promote immune evasion, permitting tumor growth. Programmed death ligand-1 (PD-L1) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and serves as a therapeutic target and predictive biomarker. Rischin, +17 authors B.1Yale University School of Medicine and Yale Cancer Center, New Haven, CTĢPeter MacCallum Cancer Centre and the University of Melbourne, Melbourne, AustraliaģParacelsus Medical University, Salzburg Cancer Research Institute, and Cancer Cluster Salzburg, Salzburg, AustriaĤCentre Hospitalier de l'Université de Montréal, Montreal, Quebec, CanadaĥNational Cancer Center Hospital East, Kashiwa, JapanĦInstituto do Cancer do Estado de Sao Paulo, Sao Paulo, BrazilħNational Kapodistrian University of Athens, Attikon University Hospital, Athens, GreeceĨVall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, SpainĩUniversity of Kansas Medical Center, Kansas City, KSġ1Medical University of Vienna, Vienna, Austriaġ2Royal Brisbane and Women's Hospital and University of Queensland, Brisbane, Queensland, Australiaġ3Catalan Institute of Oncology, Badalona, Barcelona, Spainġ4Ramathibodi Hospital, Mahidol University, Bangkok, Thailandġ5University Hospital, Zurich, Switzerlandġ6Clinical Oncology Unit, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysiaġ8The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, National Institute for Health Research Biomedical Research Centre, London, United Kingdom Progression after the next line of therapy following pembrolizumab (P) or P plus chemotherapy (P+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).},Īuthor=, KEYNOTE-048: Progression after the next line of therapy following pembrolizumab (P) or P plus chemotherapy (P+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). ![]()
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