Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi, Japan.
Department of Respiratory Medicine, Fujita Health University School of Medicine, Toyoake, Japan.
Int J Clin Oncol. 2022 Dec;27(12):1828-1838. doi: 10.1007/s10147-022-02232-7. Epub 2022 Aug 29.
We evaluated the safety and efficacy of the anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) brigatinib in Japanese patients with TKI-naive ALK-positive non-small cell lung cancer (NSCLC) from the phase 2, open-label, single-arm, multicenter J-ALTA study.
In the TKI-naive cohort of J-ALTA, the primary end point was independent review committee (IRC)-assessed 12-month progression-free survival (PFS). Secondary end points included objective response rate (ORR), intracranial response, overall survival (OS), and safety.
The data were cut approximately 12 months after last patient enrollment. Thirty-two patients with ALK TKI-naive ALK-positive NSCLC were enrolled (median age [range], 60.5 [29-85] years; median duration of follow-up, 14.2 [3.2-19.3] months; median treatment duration, 13.8 [0.4-19.3] months). IRC-assessed 12-month PFS was 93.0% (90% confidence interval (CI) 79.2-97.8%); ORR, 96.9% (95% CI 83.8-99.9%), 12-month OS, 96.9% (95% CI 79.8-99.6%), and median OS was not reached. Of five patients with measurable baseline CNS metastases, two had partial intracranial response. The most common treatment-emergent adverse events were increased blood creatine phosphokinase (81%), hypertension (59%), and diarrhea (47%). Grade ≥ 3 adverse events occurred in 91% of patients; pneumonitis was reported in 3 (9%) patients.
In the J-ALTA TKI-naive cohort, brigatinib demonstrated clinically meaningful efficacy consistent with the international phase 3 study. The safety profile in Japanese patients was consistent with previous studies. Brigatinib is an important first-line option for Japanese patients with ALK-positive NSCLC.
NCT03410108.
我们评估了间变性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂（TKI）布加替尼在来自 II 期、开放标签、单臂、多中心 J-ALTA 研究的初治 ALK 阳性非小细胞肺癌（NSCLC）日本患者中的安全性和疗效。
在 J-ALTA 的初治队列中，主要终点是独立审查委员会（IRC）评估的 12 个月无进展生存期（PFS）。次要终点包括客观缓解率（ORR）、颅内缓解、总生存期（OS）和安全性。
数据在最后一名患者入组后大约 12 个月时进行了截尾。入组 32 例初治 ALK 阳性 ALK 阳性 NSCLC 患者（中位年龄[范围]，60.5[29-85]岁；中位随访时间，14.2[3.2-19.3]个月；中位治疗时间，13.8[0.4-19.3]个月）。IRC 评估的 12 个月 PFS 为 93.0%（90%置信区间[CI]79.2-97.8%）；ORR 为 96.9%（95%CI83.8-99.9%），12 个月 OS 为 96.9%（95%CI79.8-99.6%），中位 OS 未达到。基线时有可测量的中枢神经系统转移的 5 例患者中，有 2 例有部分颅内缓解。最常见的治疗相关不良事件为血肌酸磷酸激酶升高（81%）、高血压（59%）和腹泻（47%）。91%的患者发生了≥3 级不良事件；3（9%）例患者报告了肺炎。
在 J-ALTA 初治队列中，布加替尼显示出与国际 III 期研究一致的有临床意义的疗效。日本患者的安全性与既往研究一致。布加替尼是 ALK 阳性 NSCLC 日本患者的重要一线选择。
NCT03410108。
