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
Laura Q.M. Chow, University of Washington, Seattle Cancer Care Alliance, Seattle, WA; Robert Haddad, Dana-Farber Cancer Institute, Boston, MA; Shilpa Gupta and Amit Mahipal, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ranee Mehra, Fox Chase Cancer Center, Philadelphia, PA; Joseph Paul Eder and Barbara Burtness, Yale University Cancer Center, New Haven, CT; Hyunseok Kang, Johns Hopkins University, Baltimore, MD; Jared Weiss, Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill, NC; Amy Meister, Marisa Dolled-Filhart, Kumudu Pathiraja, and Jonathan D. Cheng, Merck, Kenilworth, NJ; Tanguy Y. Seiwert, The University of Chicago, Chicago, IL; Makoto Tahara, National Cancer Center Hospital East, Kashiwa; Kei Muro, Aichi Cancer Center Hospital, Nagoya, Japan; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Sourasky Medical Center, Tel-Aviv, Israel; Se-Hoon Lee and Bhumsuk Keam, Seoul National University Hospital; Hyun Cheol Chung, Yonsei University College of Medicine, Seoul, Korea; and Chia-Chi Lin, National Taiwan University Hospital, Taipei, Taiwan.
J Clin Oncol. 2016 Nov 10;34(32):3838-3845. doi: 10.1200/JCO.2016.68.1478. Epub 2016 Sep 30.
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.
在KEYNOTE-012试验中，每2周一次静脉注射10mg/kg的抗程序性死亡-1抗体帕博利珠单抗治疗，在程序性死亡配体1（PD-L1）阳性的复发和/或转移性（R/M）头颈部鳞状细胞癌（HNSCC）中显示出持久的抗肿瘤活性。本文报告了扩展队列的研究结果，该队列中HNSCC患者，无论生物标志物状态如何，均按较低的给药频率接受固定剂量的帕博利珠单抗治疗。
R/M HNSCC患者，无论PD-L1或人乳头瘤病毒状态如何，每3周静脉注射一次200mg帕博利珠单抗。每8周进行一次影像学检查。主要终点为各中心影像供应商评估的总缓解率（ORR）（实体瘤疗效评价标准v1.1）和安全性。次要终点包括无进展生存期、总生存期以及缓解与PD-L1表达的相关性。接受一剂或多剂帕博利珠单抗治疗的患者纳入分析。
132例入组患者的中位年龄为60岁（范围25至84岁），83%为男性，57%接受过两种或更多线针对R/M疾病的治疗。中心影像供应商评估的ORR为18%（95%CI，12至26），研究者评估的ORR为20%（95%CI，13至28）。中位缓解持续时间未达到（范围，≥2至≥11个月）。6个月无进展生存率和总生存率分别为23%和59%。通过肿瘤和免疫细胞分析，PD-L1阳性患者与阴性患者相比，ORR有统计学意义的显著升高（22%对4%；P=0.021）。任何级别和≥3级的治疗相关不良事件分别发生在62%和9%的患者中。
每3周一次静脉注射200mg固定剂量的帕博利珠单抗耐受性良好，产生了具有临床意义的ORR且有持久缓解的证据，这支持该方案在晚期HNSCC患者中的进一步研发。
