Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: Results from the phase Ib KEYNOTE-012 expansion cohort

Laura Q.M. Chow, Robert Haddad, Shilpa Gupta, Amit Mahipal, Ranee Mehra, Makoto Tahara, Raanan Berger, Joseph Paul Eder, Barbara Burtness, Se Hoon Lee, Bhumsuk Keam, Hyunseok Kang, Kei Muro, Jared Weiss, Ravit Geva, Chia Chi Lin, Hyun Cheol Chung, Amy Meister, Marisa Dolled-Filhart, Kumudu PathirajaJonathan D. Cheng, Tanguy Y. Seiwert

Research output: Contribution to journalArticle

Abstract

Purpose Treatment with pembrolizumab, an anti-programmed death-1 antibody, at 10 mg/kg administered once every 2 weeks, displayed durable antitumor activity in programmed death-ligand 1 (PD-L1) -positive recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE- 012 trial. Results from the expansion cohort, in which patients with HNSCC, irrespective of biomarker status, received a fixed dose of pembrolizumab at a less frequent dosing schedule, are reported. Patients and Methods Patients with R/M HNSCC, irrespective of PD-L1 or human papillomavirus status, received pembrolizumab 200 mg intravenously once every 3 weeks. Imaging was performed every 8 weeks. Primary end points were overall response rate (ORR) per central imaging vendor (Response Evaluation Criteria in Solid Tumors v1.1) and safety. Secondary end points included progression-free survival, overall survival, and association of response and PD-L1 expression. Patients who received one or more doses of pembrolizumab were included in analyses. Results Of 132 patients enrolled, median age was 60 years (range, 25 to 84 years), 83% were male, and 57% received two or more lines of therapy for R/M disease. ORR was 18% (95% CI, 12 to 26) by central imaging vendor and 20% (95% CI, 13 to 28) by investigator review. Median duration of response was not reached (range, ≥ 2 to ≥ 11 months). Six-month progression-free survival and overall survival rates were 23% and 59%, respectively. By using tumor and immune cells, a statistically significant increase in ORR was observed for PD-L1-positive versus -negative patients (22% v 4%; P = .021). Treatment-related adverse events of any grade and grade≥3 events occurred in 62% and 9% of patients, respectively. Conclusion Fixed-dose pembrolizumab 200 mg administered once every 3 weeks was well tolerated and yielded a clinically meaningful ORR with evidence of durable responses, which supports further development of this regimen in patients with advanced HNSCC.

Original languageEnglish (US)
Pages (from-to)3838-3845
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number32
DOIs
StatePublished - Nov 10 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Chow, L. Q. M., Haddad, R., Gupta, S., Mahipal, A., Mehra, R., Tahara, M., Berger, R., Eder, J. P., Burtness, B., Lee, S. H., Keam, B., Kang, H., Muro, K., Weiss, J., Geva, R., Lin, C. C., Chung, H. C., Meister, A., Dolled-Filhart, M., ... Seiwert, T. Y. (2016). Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: Results from the phase Ib KEYNOTE-012 expansion cohort. Journal of Clinical Oncology, 34(32), 3838-3845. https://doi.org/10.1200/JCO.2016.68.1478