Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Cancer Center, Inner Mongolia Autonomous Region People's Hospital, Huhhot, China.
Thorac Cancer. 2022 Jan;13(1):107-116. doi: 10.1111/1759-7714.14232. Epub 2021 Dec 1.
There is limited data on the clinical outcome, long-term survival and tolerability of sequential therapy of first-line crizotinib followed by alectinib in a real-world setting for Chinese patients with advanced ALK+ NSCLC.
The medical records of patients who received sequential therapy with first-line crizotinib followed by alectinib (no intermittent systemic therapy was allowed between the two ALK-TKIs) were collected from six centers in China. Combined time treatment to failure (C-TTF) was defined as the period from the start of crizotinib to the complete discontinuation of alectinib due to any cause.
A total of 61 patients were included in our study. Fifty-two patients were switched to alectinib due to disease progression, seven as a result of toxicity, and two due to patient preference. At the time of data cutoff, alectinib treatment was discontinued in 31 patients on account of disease progression while severe adverse events resulted in cessation of alectinib in another two patients. Rebiopsy was conducted in 21 patients following disease progression on alectinib in whom ALK secondary mutation was found in 13 patients. Patients with ALK secondary mutation demonstrated better PFS during treatment with subsequent ALK-TKIs compared with those without (10.4 vs. 3.1 m, p = 0.0018, HR = 0.08). With a median follow-up of 34.3 months, C-TTF was 39.2 months and estimated 5-year OS was 68.6% in the overall population.
Sequential therapy with first-line crizotinib followed by alectinib demonstrated long-term benefits. Different efficacy in subsequent ALK-TKI between patients with or without ALK secondary mutation further emphasized the importance of rebiopsy to guide targeted therapy more precisely.
在真实环境中，对于中国晚期 ALK+ NSCLC 患者，一线克唑替尼序贯阿来替尼治疗的临床结局、长期生存和耐受性的数据有限。
从中国的 6 个中心收集了接受一线克唑替尼序贯阿来替尼（两种 ALK-TKI 之间不允许进行间歇性全身治疗）治疗的患者的病历。联合时间治疗失败（C-TTF）定义为从克唑替尼开始到因任何原因完全停止阿来替尼的时间段。
共有 61 例患者纳入本研究。52 例患者因疾病进展而转为阿来替尼治疗，7 例因毒性，2 例因患者偏好。在数据截止时，由于疾病进展，31 例患者停止了阿来替尼治疗，另有 2 例因严重不良事件而停止了阿来替尼治疗。在阿来替尼治疗进展的 21 例患者中进行了再次活检，其中 13 例患者发现了 ALK 继发突变。与无继发突变的患者相比，继发突变的患者在后续 ALK-TKIs 治疗期间的 PFS 更好（10.4 对 3.1 m，p=0.0018，HR=0.08）。中位随访 34.3 个月，总人群的 C-TTF 为 39.2 个月，估计 5 年 OS 为 68.6%。
一线克唑替尼序贯阿来替尼治疗具有长期获益。继发突变的患者与无继发突变的患者在后续 ALK-TKI 中的疗效不同，进一步强调了再次活检以更精确地指导靶向治疗的重要性。
