FDA批准Regorafenib治疗转移性结直肠癌

Regorafenib是一种口服多激酶抑制剂，9月27日，美国食品与药物管理局(FDA)宣布，已批准将其用于治疗转移性结直肠癌。批准的适应证为治疗转移性结直肠癌患者，“这些患者之前已接受氟嘧啶、奥沙利铂和伊立替康为基础的化疗、1种抗VEGF治疗，此外，如为KRAS野生型，已接受1种抗EGFR治疗。”

经由FDA针对重大治疗进展或无充分治疗疾病的新药的审查程序，Regorafenib在生产商提交上市申请后6个月内通过审批。这项审批是基于一项包含760例经治转移性结直肠癌患者的研究结果。随机分配到regorafenib加最佳支持治疗组的患者，中位总生存时间为6.4个月，而接受安慰剂加最佳支持治疗的患者的中位生存时间仅为5个月。Regorafenib组和安慰剂组的中位无进展生存时间分别为2个月和1.7个月。

6月份，CORRECT试验的研究者、比利时鲁汶大学Gasthuisberg医院的Eric Van Cutsem博士在美国临床肿瘤学会(ASCO)年会上报告，对于KRAS突变和KRAS野生型患者，regorafenib治疗均可延长生存期。“对于现有标准治疗失败的转移性结直肠癌患者，Regorafenib治疗可延长总生存期和无进展生存期。在各个预先设定的亚组中，均显示出这种益处。”

FDA在声明中指出，与regorafenib治疗相关的最常见不良反应包括虚弱或疲劳、食欲减退、肢端红肿症、腹泻、黏膜炎、体重减轻、感染、高血压和发声困难。临床试验中，有与治疗相关的严重肝脏毒性病例和死亡病例报告，这将在药物说明书中进行加框警告。

Regorafenib“是最新的一种可延长患者生命的结直肠癌治疗药物，并且是过去2个月内通过审批的第二种结直肠癌患者治疗药物，”FDA药物评估与研究中心血液与肿瘤产品办公室主任Richard Pazdur博士在声明中说。8月份，FDA批准ziv-aflibercep(Zaltrap)与FOLFIRI(亚叶酸、氟尿嘧啶和伊立替康)化疗方案联合治疗转移性结直肠癌。

拜耳制药公司将销售这种药物，商品名为Stivarga。推荐剂量为160 mg每日1次，在每个28天周期的前21天使用。

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By: ELIZABETH MECHCATIE, Internal Medicine News Digital Network

Regorafenib, an oral multikinase inhibitor, has been approved to treat metastatic colorectal cancer, the Food and Drug Administration announced on Sept. 27. 

The approved indication is for the treatment of patients with metastatic colorectal cancer, "who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy." 

 

Approval was based on the results of one study of 760 patients with metastatic colorectal cancer, who had been treated previously. Among those randomized to treatment with regorafenib and best supportive care, median overall survival was 6.4 months, compared with a median of 5 months among those who received placebo and best supportive care. Median progression-free survival was 2 months among those on regorafenib, compared with 1.7 months among those on placebo, according to the FDA statement announcing the approval. 

In June, CORRECT trial investigator Dr. Eric Van Cutsem of University Hospital Leuven in Gasthuisberg, Belgium, reported that regorafenib improved survival in patients with KRAS mutations as well as those with wild-type KRAS. "Regorafenib increases overall survival and progression-free survival in patients with metastatic colorectal cancer who have failed current standard therapies. The benefit is shown across prespecified subgroups," he said at the American Society of Clinical Oncology annual meeting. 

Bayer HealthCare Pharmaceuticals will market the drug as Stivarga. The recommended dose is 160 mg, once daily for the first 21 days of each 28-day cycle. 

Regorafenib "is the latest colorectal cancer treatment to demonstrate an ability to extend patients’ lives and is the second drug approved for patients with colorectal cancer in the past 2 months," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, said in the statement. 

In August, the FDA approved ziv-aflibercept (Zaltrap) for use in combination with a FOLFIRI (folinic acid, fluorouracil, and irinotecan) chemotherapy regimen for metastatic colorectal cancer. . 

The most common adverse effects associated with regorafenib treatment included weakness or fatigue, loss of appetite, palmar-plantar erythrodysesthesia, diarrhea, mucositis, weight loss, infection, hypertension, and dysphonia, the FDA said. 

In clinical trials, there were severe and fatal cases of hepatotoxicity associated with treatment, which will be highlighted in the boxed warning in the drug’s label, the FDA said. 

Regorafenib was approved within 6 months of the company’s application for approval, under the FDA’s review program for drugs that provide a major advance in treatment or provide a treatment for a disease for which there is no adequate treatment. 

Click here to view the drug’s label. 

学科代码：消化病学 肿瘤学 药学　　　关键词：Regorafenib治疗转移性结直肠癌
来源： EGMN