INTRODUCTION The phase II, single-arm ASCEND-3 study assessed efficacy and safety of ceritinib in anaplastic lymphoma kinase (ALK) inhibitor (ALKi)-naïve patients with ALK-rearranged non-small-cell lung cancer (NSCLC) who had received ≤ 3 prior lines of chemotherapy. Here, we report the final efficacy and safety results. METHODS Eligible patients (including those with asymptomatic or neurologically stable brain metastases [BM]) received oral ceritinib 750 mg/day (fasted). Primary endpoint: investigator-assessed overall response rate (ORR). Secondary endpoints: Blinded Independent Review Committee (BIRC)-assessed ORR; investigator- and BIRC-assessed overall intracranial response rate, duration of response (DOR), time to response, disease control rate, and progression-free survival (PFS); overall survival (OS); and safety. Exploratory endpoints: patient-reported outcomes. RESULTS Of the 124 patients enrolled, 122 (98.4%) had received prior antineoplastic medications (31 patients [25.0%], ≥ 3 regimens), and 49 (39.5%) had baseline BM. Median follow-up time (data cutoff: January 22, 2018): 52.1 months (range, 48.4-60.1). Investigator-assessed ORR was 67.7% (95% CI, 58.8 to 75.9) and median PFS was 16.6 months (95% CI, 11.0 to 23.2). Median OS was 51.3 months (95% CI, 42.7 to 55.3). Most common adverse events (AEs [all grades], ≥ 60% of patients, all-causality): diarrhea (85.5%), nausea (78.2%), and vomiting (71.8%). Overall, 18 patients (14.5%) had an AE leading to treatment discontinuation. Health-related quality of life was maintained during ceritinib treatment. CONCLUSION Ceritinib demonstrated prolonged and clinically meaningful OS, PFS, and DOR in chemotherapy pretreated (≤ 3 lines), ALKi-naïve patients with ALK+ NSCLC. The safety profile is consistent with that of previously reported studies.

中文翻译：

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ASCEND-3 的最终总生存期、其他疗效和安全性结果：色瑞替尼在 ALK 初治的 ALK 重排非小细胞肺癌患者中的 II 期研究

引言 II 期单臂 ASCEND-3 研究评估了色瑞替尼在未接受 ALK 重排非小细胞肺癌 (NSCLC) 的间变性淋巴瘤激酶 (ALK) 抑制剂 (ALKi) 患者中的疗效和安全性，这些患者接受了≤ 3 行先前的化疗。在这里，我们报告最终的疗效和安全性结果。方法 符合条件的患者（包括无症状或神经系统稳定的脑转移 [BM]）接受口服色瑞替尼 750 mg/天（禁食）。主要终点：研究者评估的总体反应率（ORR）。次要终点：盲法独立审查委员会 (BIRC) 评估的 ORR；研究者和 BIRC 评估的总体颅内缓解率、缓解持续时间 (DOR)、缓解时间、疾病控制率和无进展生存期 (PFS)；总生存期（OS）；和安全。探索性终点：患者报告的结果。结果 在纳入的 124 名患者中，122 名 (98.4%) 曾接受过抗肿瘤药物治疗（31 名患者 [25.0%]，≥ 3 个方案），49 名 (39.5%) 有基线 BM。中位随访时间（数据截止日期：2018 年 1 月 22 日）：52.1 个月（范围，48.4-60.1）。研究人员评估的 ORR 为 67.7%（95% CI，58.8 至 75.9），中位 PFS 为 16.6 个月（95% CI，11.0 至 23.2）。中位 OS 为 51.3 个月（95% CI，42.7 至 55.3）。最常见的不良事件（AE [所有级别]，≥ 60% 的患者，全因）：腹泻 (85.5%)、恶心 (78.2%) 和呕吐 (71.8%)。总体而言，18 名患者 (14.5%) 发生了导致治疗中断的 AE。色瑞替尼治疗期间保持了健康相关的生活质量。结论 色瑞替尼在化疗预处理（≤ 3 行）中显示出延长且具有临床意义的 OS、PFS 和 DOR，ALK 初治的 ALK+ NSCLC 患者。安全性特征与先前报告的研究一致。