Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score

Burtness, B; Rischin, D; Greil, R; Soulieres, D; Tahara, M; de Castro, G, Jr; Psyrri, A; Brana, I; Baste, N; Neupane, P; Bratland, A; Fuereder, T; Hughes, BGM; Mesia, R; Ngamphaiboon, N; Rordorf, T; Wan Ishak, WZ; Ge, J; Swaby, RF; Gumuscu, B; Harrington, K

Author(s): Burtness, B; Rischin, D; Greil, R; Soulieres, D; Tahara, M; de Castro, G, Jr; Psyrri, A; Brana, I; Baste, N; Neupane, P; Bratland, A; Fuereder, T; Hughes, BGM; Mesia, R; Ngamphaiboon, N; Rordorf, T; Wan Ishak, WZ; Ge, J; Swaby, RF; Gumuscu, B; Harrington, K;
Details: Publication Year 2022-07-20,Volume 40,Issue #21,Page 2321-2332
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: PURPOSE: The phase III KEYNOTE-048 (ClinicalTrials.gov identifier: NCT02358031) trial of pembrolizumab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) included planned efficacy analyses in the total population and in participants with programmed death ligand-1 (PD-L1) combined positive score (CPS) >/= 1 and CPS >/= 20. To further characterize the predictive value of PD-L1 expression on outcome, we conducted efficacy analyses in the PD-L1 CPS < 1 and CPS 1-19 subgroups in KEYNOTE-048. METHODS: Participants with R/M HNSCC and no prior systemic therapy for R/M disease were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Post hoc efficacy analyses of the PD-L1 CPS < 1 and CPS 1-19 subgroups were performed. RESULTS: Of 882 participants enrolled, 128 had PD-L1 CPS < 1 and 373 had CPS 1-19. For pembrolizumab versus cetuximab-chemotherapy, the median overall survival was 7.9 versus 11.3 months in the PD-L1 CPS < 1 subgroup (hazard ratio [HR], 1.51 [95% CI, 0.96 to 2.37]) and 10.8 versus 10.1 months in the CPS 1-19 subgroup (HR, 0.86 [95% CI, 0.66 to 1.12]). For pembrolizumab-chemotherapy versus cetuximab-chemotherapy, the median overall survival was 11.3 versus 10.7 months in the PD-L1 CPS < 1 subgroup (HR, 1.21 [95% CI, 0.76 to 1.94]) and 12.7 versus 9.9 months in the CPS 1-19 subgroup (HR, 0.71 [95% CI, 0.54 to 0.94]). CONCLUSION: Increased efficacy of pembrolizumab or pembrolizumab-chemotherapy was observed with increasing PD-L1 expression. PD-L1 CPS < 1 subgroup analysis was limited by small participant numbers. Results from the PD-L1 CPS 1-19 subgroup support previous findings of treatment benefit with pembrolizumab monotherapy and pembrolizumab-chemotherapy in patients with PD-L1 CPS >/= 1 tumors. Although PD-L1 expression is informative, exploration of additional predictive biomarkers is needed for low PD-L1-expressing HNSCC.
Keywords: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; *B7-H1 Antigen/metabolism; Cetuximab/therapeutic use; *Head and Neck Neoplasms/drug therapy; Humans; Neoplasm Recurrence, Local/pathology; Squamous Cell Carcinoma of Head and Neck/drug therapy
Department(s): Medical Oncology
PubMed ID: 35333599
Publisher's Version: https://doi.org/10.1200/JCO.21.02198
Open Access at Publisher's Site: https://doi.org/10.1200/jco.21.02198
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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Last Modified: 2024-10-11 04:26:13