FDA批准第二个ALK酪氨酸激酶抑制剂用于晚期肺癌

美国食品药品管理局（FDA）4月29日宣布，间变性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂ceritinib已获准用于治疗对克唑替尼不能耐受或出现疾病进展的转移性ALK阳性非小细胞肺癌（NSCLC）。

FDA声明指出，ceritinib获批是基于一项开放性研究中患者的肿瘤应答率和应答持续时间。该研究纳入163例转移性ALK阳性NSCLC患者，他们在接受克唑替尼治疗期间出现疾病进展或不能耐受克唑替尼治疗，全部接受ceritinib治疗。约半数患者肿瘤缩小，疗效中位持续时间约为7个月。

FDA加速批准了ceritinib。按照加速批准程序，如果基于临床数据，一种药物对能够预示患者临床获益的替代终点有效，可获准用于治疗严重或危及生命的疾病。不过，FDA要求制造商开展临床试验以证实患者获益。

该药物最常见的副作用包括腹泻、恶心、呕吐、腹痛以及转氨酶升高。推荐剂量为750 mg，每日1次，规格为150 mg胶囊。该药物将由诺华公司以商品名Zykadia上市销售。

该药物处方信息中包括了一项有关“改善生存期或疾病相关症状尚未得到确认，对该适应症的后续批准将视证实性试验能否确认患者临床获益而定”的声明。

克唑替尼（商品名Xalkori）是FDA批准的另一种ALK酪氨酸激酶抑制剂，批准时间为2011年。

FDA声明指出，据美国国家癌症研究所估计，NSCLC约占肺癌的85%，其中仅2%~7%为ALK阳性。预计美国今年将新增肺癌患者约224,210例，肺癌死亡病例约159,260例。

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By: ELIZABETH MECHCATIE, Oncology Practice Digital Network

 Ceritinib, an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor, has been approved for the treatment of metastatic ALK-positive non–small cell lung cancer, in patients who have progressed on or are intolerant to crizotinib, the Food and Drug Administration announced on April 29.

The accelerated approval of ceritinib, marketed as Zykadia by Novartis, was based on the tumor response rate and duration of the response in an open label study of 163 people with metastatic ALK-positive non–small cell lung cancer (NSCLC), who had progressed during treatment with crizotinib or had not tolerated the drug; all were treated with ceritinib. Tumors shrunk in about half of the patients, an effect that lasted for a median of about 7 months, according to the FDA statement announcing the approval.

The most common side effects of the drug include diarrhea, nausea, vomiting,and abdominal pain; and elevated transaminases. The recommended dose is 750-mg dose once a day. It is available in 150-mg capsules.

Crizotinib, marketed as Xalkori, is the only other ALK tyrosine kinase inhibitor approved by the FDA; it was approved in 2011.

The FDA is approving ceritinib under the agency’s accelerated approval program, through which a drug can be approved to treat a serious or life-threatening disease based on clinical data showing effects on a surrogate endpoint that is "reasonably likely to predict clinical benefit." The manufacturer is required to conduct clinical trials to confirm the results.

The drug’s prescribing information includes the statement that "an improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials."

The FDA statement cited National Cancer Institute estimates that NSCLC accounts for about 85% of lung cancers, of which only 2%-7% are ALK positive. This year, about 224,210 people in the United States will be diagnosed with lung cancer and about 159,260 people will die from lung cancer, according to NCI.