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Chow LQM , Haddad R , Gupta S , Mahipal A , Mehra R , Tahara M , Berger R , Eder JP , Burtness B , Lee SH , Keam B , Kang H , Muro K , Weiss J , Geva R , Lin CC , Chung HC , Meister A , Dolled-Filhart M , Pathiraja K , Cheng JD , Seiwert TY
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
J Clin Oncol. 2016 Nov 10;34(32) :3838-3845
PMID: 27646946    PMCID: PMC6804896    URL: https://www.ncbi.nlm.nih.gov/pubmed/27646946
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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.
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 eng Multicenter Study J Clin Oncol. 2016 Nov 10;34(32):3838-3845. doi: 10.1200/JCO.2016.68.1478. Epub 2016 Sep 30.