Background: Second-line treatment options for advanced head and neck squamous cell carcinoma (HNSCC) are limited. The phase Ib KEYNOTE-012 study evaluated the safety and the efficacy of pembrolizumab for the treatment of HNSCC after long-term follow-up. Methods: Multi-centre, non-randomised trial included two HNSCC cohorts (initial and expansion) in which 192 patients were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks (initial cohort; N = 60) or 200 mg every 3 weeks (expansion cohort; N = 132). Co-primary endpoints were safety and overall response rate (ORR; RECIST v1.1; central imaging vendor review). Results: Median follow-up was 9 months (range, 0.2-32). Treatment-related adverse events (AEs) of any grade and grade 3/4 occurred in 123 (64%) and 24 (13%) patients, respectively. No deaths were attributed to treatment-related AEs. ORR was 18% (34/192; 95% CI, 13-24%). Median response duration was not reached (range, 2+ to 30+ months); 85% of responses lasted ≥6 months. Overall survival at 12 months was 38%. Conclusions: Some patients received 2 years of treatment and the responses were ongoing for more than 30 months; the durable anti-tumour activity and tolerable safety profile, observed with long-term follow-up, support the use of pembrolizumab as a treatment for recurrent/metastatic HNSCC.
Bibliographical noteFunding Information:
We thank the patients and their families, and caregivers for participating in the study. We also thank Jennifer Yearley of Merck & Co., Inc., Kenilworth, NJ, USA, for her contributions to this research. Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, Dana Francis, PhD, and the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co., Inc., Kenilworth, NJ, USA.
The study was designed and funded by Merck & Co., Inc., Kenilworth, NJ, USA. R.M., T. Y.S., J.W., I.G., J.P.E., B.B., M.T., B.K., H.K., M.K., H.C.C., C.C.L., A.R., K.P., L.Q.W., and R.H. collected the data. R.M., J.W., B.B., H.C.C., D.A.-G., K.P., J.C., L.Q.W., and R.H. analyzed the data. R.M., T.Y.S., J.W., I.G., B.B., M.T., B.K., H.K., H.C.C., C.C.L., K.P., J.C., L.Q.W., and R. H. contributed to the interpretation of the results. R.M., M.T., and K.P. contributed to drafting of the manuscript.
Competing interests: T.Y.S., J.W., B.B., and H.K. have received research funding from Merck & Co., Inc. M.T. has received personal fees from Merck Sharp & Dohme. D.A.-G., A.R., K.P., and J.C. are employees Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. L.Q.C. has served as an advisor for and has received research from Merck & Co., Inc. R.H. has received research funding from Merck & Co., Inc., Bristol-Myers Squibb, Pfizer, and Astra Zeneca, and has served as a consultant for Merck & Co., Inc., Bristol-Myers Squibb, Pfizer, Celgene, Astra Zeneca, and Eisai. The remaining authors declare no competing interests.
All Science Journal Classification (ASJC) codes
- Cancer Research