Clinical efficacy of crizotinib in Chinese patients with ALK-positive non-small-cell lung cancer with brain metastases
Clinical efficacy of crizotinib in Chinese patients with ALK-positive non-small-cell lung cancer with brain metastases
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DOI：
10.3978/j.issn.2072-1439.2015.06.04
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发表时间：
2015-07-01
影响因子：
2.5
通讯作者：
Wu, Yi-Long
中科院分区：
文献类型：
--
作者：
Lei, Yuan-Yuan;Yang, Jin-Ji;Wu, Yi-Long
背景：克唑替尼与间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌（NSCLC）脑转移患者的颅内疾病控制相关。持续的克唑替尼治疗也被用于对患有孤立性中枢神经系统（CNS）衰竭的患者进行长期疾病控制。然而，克唑替尼对中国 ALK 阳性患者疗效的研究很少。因此，我们回顾性研究了克唑替尼在中国基线时患有脑转移的 ALK 阳性 NSCLC 患者中的临床疗效，并评估了中枢神经系统衰竭后继续使用克唑替尼的临床获益。 方法：共纳入 120 例接受克唑替尼治疗的晚期 ALK 阳性 NSCLC 患者，其中 38 例基线时患有脑转移。比较基线时有脑转移和无脑转移的患者的客观缓解率（ORR）和无进展生存期（PFS）。一部分发生中枢神经系统衰竭的患者在疾病进展 (PD) 后继续接受克唑替尼治疗，并且还评估了自第一次进展时起的第二次 PFS。 结果：基线时有脑转移和无脑转移的患者之间克唑替尼的 ORR 相似（68.4% vs. 69.5%，P=0.904）。然而，基线时没有脑转移的患者的中位 PFS 较长 [10.0 个月，95% 置信区间 (CI)，7.6-12.5 vs. 7.0 个月，95% CI，6.4-7.6； P=0.021]。在定义实体瘤疗效评估标准 (RECIST) 的 88 名 PD 患者中，33 名出现中枢神经系统衰竭。共有 24 名发生 CNS 衰竭的患者在 PD 后继续接受克唑替尼治疗，他们的第二中位 PFS 为 6.3 个月（95% CI，2.9-9.7）。 结论：中国患有脑转移的 ALK 阳性 NSCLC 患者对克唑替尼的反应相似，与基线时无脑转移的患者相比，PFS 显着缩短。对于发生中枢神经系统衰竭的患者，在 PD 后持续给予克唑替尼似乎是一种有效的治疗策略。
Background: Crizotinib has been associated with intracranial disease control in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients with brain metastases. Continued crizotinib treatment has also been used for prolonged disease control in patients experiencing isolated central nervous system (CNS) failure. However, there are few studies of crizotinib efficacy in ALK-positive Chinese patients. Thus, we retrospectively investigated the clinical efficacy of crizotinib in Chinese ALK-positive NSCLC patients with brain metastases at baseline, and evaluated the clinical benefit of continuing crizotinib beyond CNS failure.Methods: A total of 120 advanced ALK-positive NSCLC patients treated with crizotinib were enrolled with 38 having brain metastases at baseline. The objective response rate (ORR) and progression-free survival (PFS) were compared between patients with and without brain metastases at baseline. A subset of patients who developed CNS failure continued crizotinib treatment beyond progressive disease (PD), and the second PFS from the time of the first progression was also evaluated.Results: The ORR of crizotinib was similar between patients with and without brain metastases at baseline (68.4% vs. 69.5%, P=0.904). However, the patients without brain metastases at baseline experienced a longer median PFS [10.0 months, 95% confidence interval (CI), 7.6-12.5 vs. 7.0 months, 95% CI, 6.4-7.6; P=0.021]. Among 88 patients with PD defined Response Evaluation Criteria in Solid Tumors (RECIST), 33 developed CNS failure. A total of 24 patients who developed CNS failure continued crizotinib treatment beyond PD, and they achieved a second median PFS of 6.3 months (95% CI, 2.9-9.7).Conclusions: Chinese ALK-positive NSCLC patients with brain metastases achieved a similar response to crizotinib and significantly shorter PFS compared to those without brain metastases at baseline. Continuous administration of crizotinib beyond PD in patients developing CNS failure appeared to be a valid treatment strategy.