Author(s): Marcin Dzienis, MD1; Juan Cundom, MD2; Christian Sebastian Fuentes, MD3; Anna Spreafico, MD4; Melanie Nordlinger, MD5; Andrea Viviana Pastor, MD6; Erin Alesi, MD7; Anterpreet Neki, MD8; Andrea S. Fung, MD, PhD9; Iane Pinto Figueiredo Lima, MD10; Peter Oppelt, MD11; Geraldo Felicio da Cunha Junior, PhD12; Barbara Burtness, MD13; Fabio Andre Franke, MD14; Jennifer E. Tseng, MD15; Abhishek Joshi, MD16; Joy McCarthy, MD17; Ramona Swaby, MD18; Yulia Sidi, PhD18; Burak Gumuscu, MD, PhD18; Niroshini Naicker, MD19; Gilberto de Castro Jr, MD, PhD20
PURPOSE
Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888).
METHODS
Eligible adults had previously untreated, histologically or cytologically confirmed R/M HNSCC regardless of PD-L1 status, measurable disease per RECIST v1.1 by blinded independent central review (BICR), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received pembrolizumab 200 mg intravenously once every 3 weeks for ≤35 cycles and carboplatin AUC 5 mg/mL/min intravenously once every 3 weeks for ≤6 cycles and investigator’s choice of paclitaxel 100 mg/m2 on days 1 and 8 or 175 mg/m2 on day 1, intravenously once every 3 weeks. The primary end point was objective response rate per RECIST v1.1 by BICR.
RESULTS
Between October 27, 2020, and April 29, 2022, 149 patients were screened and 101 received treatment. As of February 20, 2023, the median follow-up was 18.9 months (range, 9.1-27.0). At this final analysis, 49 (49%) of 101 patients had an objective response (95% CI, 38.4 to 58.7), including seven patients (7%) with a confirmed complete response. Of the 101 treated patients, grade 3-5 and serious treatment-related adverse events occurred in 76 (75%) and 27 (27%), respectively. There were no new safety signals.
CONCLUSION
Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line R/M HNSCC, suggesting this combination may be an alternative option for this patient population.
Author Affiliations
1Cancer Department, Gold Coast University Hospital, Southport, QLD, Australia; 2Department of Oncology, IDIM Instituto de Diagnóstico e Investigaciones Metabólicas, Buenos Aires, Argentina; 3Department of Oncology, Fundación Respirar, Buenos Aires, Argentina; 4Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto, ON, Canada; 5Department of Medical Oncology, Sidney Kimmel Cancer Center at Jefferson-Abington Hospital, Philadelphia, PA; 6Department of Oncology, Hospital Provincial del Centenario, Rosario, Argentina; 7Department of Hematology/Oncology and Palliative Medicine, VCU Massey Cancer Center, Richmond, VA; 8Department of Hematology/Oncology, UC Davis Medical Center, Sacramento, CA; 9Department of Oncology, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON, Canada; 10Department of Oncology, Centro Regional Integrado de Oncologia, Fortaleza, Brazil; 11Department of Oncology, Washington University School of Medicine, St Louis, MO; 12Department of Oncology, CETUS Oncologia, Belo Horizonte, Brazil; 13Yale University School of Medicine and Yale Cancer Center, New Haven, CT; 14Department of Oncology, Oncosite Centro de Pesquisa Clínica em Oncologia, Ijuí, Brazil; 15Department of Hematology and Oncology, Orlando Health Cancer Institute, Orlando, FL; 16Department of Medical Oncology, The Townsville University Hospital, Douglas, QLD, Australia; 17Dr. H. Bliss Murphy Cancer Centre, St John’s, NL, Canada; 18Merck & Co, Inc, Rahway, NJ; 19Oncology European Clinical Development, MSD (UK) Limited, London, United Kingdom; 20Clinical Oncology, Instituto do Câncer do Estado de São Paulo—ICESP, São Paulo, Brazil
