Thummalapalli Rohit, Choudhury Noura J, Ehrich Fiona, Beardslee Tyler, Brazel Danielle, Zhang Shannon S, Merchant Shelby, Chen Monica F, Heller Glenn, Ramalingam Suresh S, Ou Sai-Hong Ignatius, Mileham Kathryn F, Riely Gregory J
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
JTO Clin Res Rep. 2023 Jun 30;4(8):100546. doi: 10.1016/j.jtocrr.2023.100546. eCollection 2023 Aug.
Treatment with lorlatinib for patients with advanced - and -rearranged NSCLC (+ and + NSCLC) is associated with a unique set of adverse events (AEs) often requiring dose reduction. However, the impact of dose reductions on outcomes remains unclear and is mainly limited to analyses from prospective studies of lorlatinib in the first-line setting.
We reviewed the course of 144 patients with advanced or -rearranged NSCLC treated with lorlatinib in the second-line or later setting to assess the frequency of dose reductions resulting from treatment-related AEs (TRAEs) and the association between dose reductions and progression-free survival (PFS) and overall survival (OS).
A total of 58 patients (40%) had TRAE-related dose reductions, most (59%) owing to neurocognitive AEs or neuropathy. Among all patients, the median PFS was 8.1 months (95% confidence interval [CI]: 6.4-11.8); the median OS was 20.7 months (95% CI: 16.3-30.5). Among patients who were started on lorlatinib 100 mg/d (n = 122), a Cox regression model with the occurrence of a dose reduction as a time-dependent covariate indicated no association between dose reduction and PFS (hazard ratio = 0.86, 95% CI: 0.54-1.39) or OS (hazard ratio = 0.78, 95% CI: 0.47-1.30).
Lorlatinib dose reductions were not associated with inferior clinical outcomes in this multicenter analysis. Prompt identification of lorlatinib TRAEs and implementation of dose reductions may help maximize tolerability without compromising outcomes.
使用劳拉替尼治疗晚期ALK重排非小细胞肺癌（ALK+和ROS1+非小细胞肺癌）患者会出现一系列独特的不良事件（AE），常常需要降低剂量。然而，剂量降低对治疗结果的影响仍不明确，且主要限于劳拉替尼一线治疗的前瞻性研究分析。
我们回顾了144例在二线或更晚期接受劳拉替尼治疗的晚期ALK重排或ROS1重排非小细胞肺癌患者的病程，以评估因治疗相关不良事件（TRAE）导致剂量降低的频率，以及剂量降低与无进展生存期（PFS）和总生存期（OS）之间的关联。
共有58例患者（40%）因TRAE进行了剂量降低，大多数（59%）是由于神经认知AE或神经病变。在所有患者中，中位PFS为8.1个月（95%置信区间[CI]：6.4 - 11.8）；中位OS为20.7个月（95%CI：16.3 - 30.5）。在开始使用100mg/d劳拉替尼的患者中（n = 122），以剂量降低的发生作为时间依赖性协变量的Cox回归模型表明，剂量降低与PFS（风险比 = 0.86，95%CI：0.54 - 1.39）或OS（风险比 = 0.78，95%CI：0.47 - 1.30）之间无关联。
在这项多中心分析中，劳拉替尼剂量降低与较差的临床结果无关。及时识别劳拉替尼TRAE并实施剂量降低可能有助于在不影响治疗结果的情况下最大限度地提高耐受性。
