FDA完全批准克唑替尼治疗NSCLC

11月21日，美国食品药品管理局(FDA)声明宣布，鉴于最新研究表明克唑替尼治疗患者的无进展生存期和总应答率均优于化疗患者，已完全批准激酶抑制剂克唑替尼(crizotinib)用于转移性非小细胞肺癌(NSCLC)的治疗。

2011年8月，FDA在批准间变性淋巴瘤激酶(ALK)检测方法的同时，加速批准了克唑替尼用于该检测方法确认的ALK阳性NSCLC的治疗。这是基于在2项单臂开放性试验中，客观应答率分别为50%和61%。而这次完全批准令则是依据新的证据进一步确认了上述临床获益。

新证据来自一项国际多中心开放性随机研究。该研究纳入了347例接受了以铂为基础的化疗后出现进展的ALK阳性转移性NSCLC患者。这些患者随机接受克唑替尼治疗或化疗，如果化疗患者此前已接受了培美曲塞治疗，则继续接受培美曲塞或多西他赛治疗。

克唑替尼组和化疗组中位无进展生存期分别为7.7个月和3.0个月，前者风险下降51%[风险比(HR)为0.49] ，差异显著。客观应答率分别为65%和20%，差异也呈显著。中位应答时间分别为7.4个月和5.6个月。不过按照计划进行的中期分析显示，两组总生存率相似。

与克唑替尼治疗相关的常见不良事件包括恶心、腹泻、呕吐、视觉障碍、便秘、水肿、转氨酶升高和疲乏，累及至少25%的治疗患者。

对172例克唑替尼治疗患者的安全性评价分析显示，37%的患者出现严重不良事件，最常见的包括肺炎、肺栓塞、呼吸困难和间质性肺病。不良事件导致9例患者死亡，包括急性呼吸窘迫综合征、心律失常、呼吸困难、肺炎、吸入性肺炎、肺栓塞、间质性肺炎、呼吸衰竭以及脓毒症。

克唑替尼将由辉瑞制药以Xalkori商品名上市，为胶囊剂型，250 mg/次，2次/日，单独或与食物同服。

克唑替尼处方信息可点击此处查阅。

与克唑替尼相关的严重不良事件应上报至FDA MedWatch不良事件报告系统或致电800-332-1088。

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By: ELIZABETH MECHCATIE, Oncology Practice

The kinase inhibitor crizotinib has received full approval for the treatment of metastatic non–small cell lung cancer, based on a study that found treatment with the drug was associated with superior progression-free survival and overall response rates compared with chemotherapy.

The Food and Drug Administration announced the approval Nov. 21 in a written statement.

In August 2011, crizotinib received accelerated approval for the treatment of metastatic non–small cell lung cancer (NSCLC) in patients whose tumors are anaplastic lymphoma kinase (ALK) positive, as detected by a test approved by the FDA at the same time. The drug approval was based on objective response rates of 50% and 61% in two single-arm open-label trials; full approval was contingent on providing evidence that confirmed the clinical benefits.

This evidence was provided by an open-label, multinational randomized study of 347 patients with ALK-positive metastatic NSCLC, who had progressed after treatment with platinum-based chemotherapy. The patients were randomized to treatment with crizotinib or chemotherapy, according to the statement. Those who received chemotherapy received pemetrexed or docetaxel if they previously had been treated with pemetrexed.

The median progression-free survival was 7.7 months among those on crizotinib, compared with 3.0 months among those on chemotherapy, a statistically significant difference that represented a reduced risk of 51% (hazard ratio = 0.49). The objective response rate was 65% among those on crizotinib, compared with 20% of those on chemotherapy, also a significant difference. The median response durations were 7.4 months and 5.6 months, respectively. In a planned interim analysis, however, overall survival was the same in both groups, according to the FDA.

Common adverse events associated with crizotinib, affecting at least 25% of treated patients, included nausea, diarrhea, vomiting, visual disorders, constipation, edema, elevated transaminase levels, and fatigue.

In a safety evaluation of 172 patients treated with crizotinib in the study, 37% had serious adverse events, the FDA said. Pneumonia, pulmonary embolism, dyspnea, and interstitial lung disease were the most common. Adverse events, which included acute respiratory distress syndrome, arrhythmia, dyspnea, pneumonia, pneumonitis, pulmonary embolism, interstitial lung disease, respiratory failure, and sepsis, were fatal in nine patients.

Crizotinib is marketed as Xalkori, by Pfizer. It comes in a capsule formulation and is administered at a dose of 250 mg, twice a day, with or without food.

The prescribing information is available here.

Serious adverse events associated with crizotinib should be reported to the FDA’s MedWatch program at 800-332-1088 or here.