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

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

来源：Journal of Clinical Oncology, 2016, 34(32): 3838-+.

DOI：10.1200/JCO.2016.68.1478

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.

• 出版日期2016-11-10