Introduction: The phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first‐line chemotherapy in prolonging progression‐free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)‐positive advanced nonsquamous NSCLC. This result was consistent with that in the smaller subset of East Asian patients in PROFILE 1014. The subsequent study reported here prospectively evaluated crizotinib in a larger East Asian patient population. Methods: In this open‐label phase III study (PROFILE 1029), patients were randomized 1:1 to receive orally administered crizotinib 250 mg twice daily continuously (3‐week cycles) or intravenously administered chemotherapy (pemetrexed 500 mg/m2, plus cisplatin 75 mg/m2, or carboplatin [at a dose to produce area under the concentration–time curve of 5–6 mg·min/mL]) every 3 weeks for a maximum of six cycles. PFS confirmed by independent radiology review was the primary end point. Results: Crizotinib significantly prolonged PFS (hazard ratio, 0.402; 95% confidence interval [CI]: 0.286–0.565; p < 0.001). The median PFS was 11.1 months with crizotinib and 6.8 months with chemotherapy. The objective response rate was 87.5% (95% CI: 79.6–93.2%) with crizotinib versus 45.6% (95% CI: 35.8–55.7%) with chemotherapy (p < 0.001). The most common adverse events were increased transaminase levels, diarrhea, and vision disorders with crizotinib and leukopenia, neutropenia, and anemia with chemotherapy. Significantly greater improvements from baseline in patient‐reported outcomes were seen in crizotinib‐treated versus chemotherapy‐treated patients. Conclusions: First‐line crizotinib significantly improved PFS, objective response rate, and patient‐reported outcomes compared with standard platinum‐based chemotherapy in East Asian patients with ALK‐positive advanced NSCLC, which is similar to the results from PROFILE 1014. The safety profiles of crizotinib and chemotherapy were consistent with those previously published.

中文翻译：

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PROFILE 1029 的结果，在东亚 ALK 阳性晚期非小细胞肺癌患者中一线克唑替尼与化疗的 III 期比较

简介：III 期随机 PROFILE 1014 研究表明，在先前未经治疗的 ALK 受体酪氨酸激酶基因 (ALK) 阳性晚期非鳞状 NSCLC 患者中，克唑替尼在延长无进展生存期 (PFS) 方面优于一线化疗。这一结果与 PROFILE 1014 中较小的东亚患者亚组中的结果一致。随后的研究报告在更大的东亚患者群体中前瞻性地评估了克唑替尼。方法：在这项开放标签的 III 期研究 (PROFILE 1029) 中，患者按 1:1 随机分配接受口服克唑替尼 250 mg 每天两次（3 周周期）或静脉内给药的化疗（培美曲塞 500 mg/m2，加顺铂） 75 毫克/平方米，或卡铂 [以产生 5–6 mg·min/mL 的浓度-时间曲线下面积的剂量]）每 3 周一次，最多六个周期。经独立放射学审查确认的 PFS 是主要终点。结果：克唑替尼显着延长了 PFS（风险比，0.402；95% 置信区间 [CI]：0.286–0.565；p < 0.001）。克唑替尼组的中位 PFS 为 11.1 个月，化疗组为 6.8 个月。克唑替尼的客观缓解率为 87.5%（95% CI：79.6-93.2%），而化疗为 45.6%（95% CI：35.8-55.7%）（p < 0.001）。最常见的不良事件是转氨酶水平升高、腹泻和克唑替尼导致的视力障碍和白细胞减少症、中性粒细胞减少症和化疗导致的贫血。在接受克唑替尼治疗的患者与接受化疗的患者中，患者报告的结果较基线显着改善。结论：在东亚 ALK 阳性晚期 NSCLC 患者中，与标准铂类化疗相比，一线克唑替尼可显着改善 PFS、客观缓解率和患者报告结果，这与 PROFILE 1014 的结果相似。克唑替尼和化疗的疗效与先前发表的一致。