Cheung Justin M, Kang Jiyoon, Yeap Beow Y, Peterson Jennifer L, Do Andrew, Gainor Justin F, Digumarthy Subba R, Lin Jessica J
Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts.
Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
JTO Clin Res Rep. 2024 Feb 1;5(3):100645. doi: 10.1016/j.jtocrr.2024.100645. eCollection 2024 Mar.
Central nervous system (CNS) metastases remain a common challenge in patients with ALK-positive NSCLC. We previously reported reinduction of CNS responses using dose-intensified alectinib in two patients with CNS progression on standard-dose alectinib. Nevertheless, this strategy has not been assessed in larger cohorts.
Patients were eligible for this retrospective study if they had metastatic ALK-positive NSCLC with CNS relapse on alectinib 600 mg twice daily dosing and subsequently received escalated dosing (900 mg twice daily) of alectinib. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1.
Among 27 patients, median duration of dose-escalated alectinib was 7.7 months (95% confidence interval [CI]: 4.8-10.9), with median overall time-to-progression (TTP) of 7.1 months (95% CI: 4.4-9.6). Among 25 CNS response-assessable patients, CNS objective response rate was 12.0% (95% CI: 2.5-31.2) and CNS disease control rate was 92.0% (95% CI: 74.0-99.0), with median CNS duration of disease control of 5.3 months (95% CI: 3.4-8.3) and median CNS TTP of 7.1 months (95% CI: 4.4-9.6). Among four patients with measurable CNS disease at baseline, three experienced a best intracranial response of stable disease and one experienced intracranial partial response with CNS TTP ranging from 4.1 to 7.7 months. No patient required drug discontinuation due to treatment-related adverse event or experienced grade 3 or higher treatment-related adverse events.
Dose-intensified alectinib was found to have tolerability and activity in patients with ALK-positive NSCLC who experienced CNS relapse on standard-dose alectinib and represents one clinically viable strategy for this population.
中枢神经系统（CNS）转移仍然是ALK阳性非小细胞肺癌（NSCLC）患者面临的常见挑战。我们之前报道了在两名接受标准剂量阿来替尼治疗出现CNS进展的患者中，使用剂量强化的阿来替尼重新诱导CNS反应。然而，该策略尚未在更大的队列中进行评估。
如果患者患有转移性ALK阳性NSCLC，在每日两次服用600mg阿来替尼时出现CNS复发，随后接受剂量递增（每日两次900mg）的阿来替尼治疗，则符合本回顾性研究的条件。根据实体瘤疗效评价标准第1.1版对CNS疗效进行评估。
27例患者中，剂量递增的阿来替尼的中位持续时间为7.7个月（95%置信区间[CI]：4.8 - 10.9），中位总疾病进展时间（TTP）为7.1个月（95%CI：4.4 - 9.6）。在25例可评估CNS反应的患者中，CNS客观缓解率为12.0%（95%CI：2.5 - 31.2），CNS疾病控制率为92.0%（95%CI：74.0 - 99.0），CNS疾病控制的中位持续时间为5.3个月（95%CI：3.4 - 8.3），CNS TTP的中位值为7.1个月（95%CI：4.4 - 9.6）。在4例基线时CNS疾病可测量的患者中，3例最佳颅内反应为疾病稳定，1例出现颅内部分缓解，CNS TTP为4.1至7.7个月。没有患者因治疗相关不良事件而停药，也没有患者经历3级或更高等级的治疗相关不良事件。
对于在标准剂量阿来替尼治疗时出现CNS复发的ALK阳性NSCLC患者，发现剂量强化的阿来替尼具有耐受性和活性，是该人群一种临床上可行的策略。
