Larkins Erin, Scepura Barbara, Blumenthal Gideon M, Bloomquist Erik, Tang Shenghui, Biable Missiratch, Kluetz Paul, 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. 2015 Nov;20(11):1320-5. doi: 10.1634/theoncologist.2015-0221. Epub 2015 Oct 7.
On December 12, 2014, the U.S. Food and Drug Administration (FDA) approved ramucirumab for use in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving ramucirumab. This approval was based on an improvement in overall survival (OS) with an acceptable toxicity profile in a randomized, multicenter, double-blinded, placebo-controlled trial of 1,253 patients with metastatic NSCLC previously treated with a platinum-based combination therapy. Patients were randomized 1:1 to receive either ramucirumab in combination with docetaxel or placebo in combination with docetaxel. The primary endpoint was OS. Patients who received ramucirumab in combination with docetaxel had improved OS (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.75, 0.98). Median OS was 10.5 months on the ramucirumab plus docetaxel arm versus 9.1 months on the placebo plus docetaxel arm. The most frequent (≥ 30%) adverse reactions in ramucirumab-treated patients were fatigue, neutropenia, and diarrhea. The most frequent (≥ 5%) grade 3 and 4 adverse reactions in the ramucirumab arm were fatigue, neutropenia, febrile neutropenia, leukopenia, and hypertension.
This report presents key information on the U.S. Food and Drug Administration approval of ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor-2, given in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer whose disease has progressed on or after platinum-based chemotherapy. This report specifically addresses the issues of safety in patients with squamous cell tumors, effect of treatment in elderly patients, and uncertainties regarding effects in patients with tumors harboring epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.
2014年12月12日，美国食品药品监督管理局（FDA）批准雷莫西尤单抗与多西他赛联合用于治疗铂类化疗期间或之后病情进展的转移性非小细胞肺癌（NSCLC）患者。患有表皮生长因子受体或间变性淋巴瘤激酶基因组肿瘤畸变的患者，在接受雷莫西尤单抗治疗前，应在FDA批准的针对这些畸变的治疗方案中出现病情进展。该批准基于一项随机、多中心、双盲、安慰剂对照试验，该试验纳入1253例先前接受铂类联合治疗的转移性NSCLC患者，结果显示总体生存期（OS）有所改善且毒性特征可接受。患者按1:1随机分组，分别接受雷莫西尤单抗联合多西他赛或安慰剂联合多西他赛治疗。主要终点为OS。接受雷莫西尤单抗联合多西他赛治疗的患者OS得到改善（风险比[HR]：0.86；95%置信区间[CI]：0.75，0.98）。雷莫西尤单抗联合多西他赛组的中位OS为10.5个月，而安慰剂联合多西他赛组为9.1个月。雷莫西尤单抗治疗患者中最常见（≥30%）的不良反应为疲劳、中性粒细胞减少和腹泻。雷莫西尤单抗组最常见（≥5%）的3级和4级不良反应为疲劳、中性粒细胞减少、发热性中性粒细胞减少、白细胞减少和高血压。
本报告介绍了美国食品药品监督管理局批准雷莫西尤单抗的关键信息，雷莫西尤单抗是一种靶向血管内皮生长因子受体-2的单克隆抗体，与多西他赛联合用于治疗铂类化疗期间或之后病情进展的转移性非小细胞肺癌患者。本报告特别探讨了鳞状细胞肿瘤患者的安全性问题、老年患者的治疗效果以及表皮生长因子受体或间变性淋巴瘤激酶基因组肿瘤畸变患者治疗效果的不确定性。
