Larkins Erin, Blumenthal Gideon M, Yuan Weishi, He Kun, Sridhara Rajeshwari, Subramaniam Sriram, Zhao Hong, Liu Chao, Yu Jingyu, Goldberg Kirsten B, McKee Amy E, Keegan Patricia, Pazdur Richard
Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncologist. 2017 Jul;22(7):873-878. doi: 10.1634/theoncologist.2016-0496. Epub 2017 May 22.
On August 5, 2016, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp., Kenilworth, NJ) for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. Approval was based on the objective response rate (ORR) and duration of response (DoR) in a cohort of patients in a nonrandomized multi-cohort trial (KEYNOTE-012) that included 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. Patients received either intravenous pembrolizumab 10 mg/kg every 2 weeks or 200 mg every 3 weeks. ORR was determined by independent review according to Response Evaluation Criteria in Solid Tumors 1.1. ORR was 16% (95% confidence interval 11, 22) with a complete response rate of 5%. DoR ranged from 2.4+ months to 27.7+ months. Twenty-three of 28 responding patients (82%) had response durations of ≥6 months. Safety was evaluated in 192 patients with HNSCC receiving at least one dose of pembrolizumab. Frequent (≥2%) serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders. The benefit-risk profile of pembrolizumab was considered acceptable in this patient population. As a condition of accelerated approval, Merck is required to conduct a confirmatory trial; this trial, KEYNOTE-040, is ongoing.
This accelerated approval expands the U.S. Food and Drug Administration-approved indications for pembrolizumab, providing health care providers with new information regarding pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. Pembrolizumab is the first drug to receive approval for treatment of patients with HNSCC since cetuximab was approved for this indication in 2006.
2016年8月5日，美国食品药品监督管理局加速批准帕博利珠单抗（可瑞达注射剂，默克公司，新泽西州肯尼沃思）用于治疗铂类化疗期间或之后病情进展的复发或转移性头颈部鳞状细胞癌（HNSCC）患者。批准基于一项非随机多队列试验（KEYNOTE-012）中一组患者的客观缓解率（ORR）和缓解持续时间（DoR），该试验纳入了174例铂类化疗期间或之后病情进展的复发或转移性HNSCC患者。患者接受每2周静脉注射10 mg/kg帕博利珠单抗或每3周注射200 mg。ORR由独立审查根据实体瘤疗效评价标准1.1确定。ORR为16%（95%置信区间11, 22），完全缓解率为5%。DoR范围为2.4+个月至27.7+个月。28例缓解患者中有23例（82%）缓解持续时间≥6个月。对192例接受至少一剂帕博利珠单抗的HNSCC患者进行了安全性评估。常见（≥2%）严重不良反应包括肺炎、呼吸困难、意识模糊状态、呕吐、胸腔积液和呼吸衰竭。具有临床意义的免疫介导不良反应包括肺炎、结肠炎、肝炎、肾上腺功能不全、糖尿病、皮肤毒性、肌炎和甲状腺疾病。在该患者群体中，帕博利珠单抗的获益风险状况被认为是可接受的。作为加速批准的条件，默克公司必须进行一项确证性试验；该试验KEYNOTE-040正在进行中。
此次加速批准扩大了美国食品药品监督管理局批准的帕博利珠单抗适应证，为医疗服务提供者提供了有关帕博利珠单抗用于治疗铂类化疗期间或之后病情进展的复发或转移性头颈部鳞状细胞癌（HNSCC）患者的新信息。自2006年西妥昔单抗获批用于该适应证以来，帕博利珠单抗是首个获批用于治疗HNSCC患者的药物。
