Lorlatinib Tolerability and Association With Clinical Outcomes in Patients With Advanced ALK- or ROS1-Rearranged NSCLC: A Brief Report

• Type of Material: Article
• Authors: Rohit Thummalapalli, Memorial Sloan Kettering Cancer Center; Noura J. Choudhury, Memorial Sloan Kettering Cancer Center; Fiona Ehrich, Memorial Sloan Kettering Cancer Center; Tyler Beardslee, Emory University; Danielle Brazel, University of California Irvine; Shannon S. Zhang, University of California Irvine; Shelby Merchant, Levine Cancer Institute; Monica F. Chen, Memorial Sloan Kettering Cancer Center; Glenn Heller, Memorial Sloan Kettering Cancer Center; Suresh S Ramalingam, Emory University; Sai-Hong Ignatius Ou, University of California Irvine; Kathryn F. Mileham, Levine Cancer Institute; Gregory J. Riely, Memorial Sloan Kettering Cancer Center
• Language: English
• Date: 2023-06-30
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1016%2Fj.jtocrr.2023.100546
• Title of Journal or Parent Work: JTO Clinical and Research Reports
• Volume: 4
• Issue: 8
• Start Page: 100546
• Grant/Funding Information: This study was funded by the National Institute of Health grants (cancer center grant P30CA008748 to Memorial Sloan Kettering Cancer Center, T32-CA009207 to Dr. Thummalapalli) and philanthropy (grants from John and Georgia DallePezze to Memorial Sloan Kettering Cancer Center, The Ning Zhao and Ge Li Family Initiative for Lung Cancer Research and New Therapies, and the James A. Fieber Lung Cancer Research Fund).
• Keywords: ROS1; Non–small cell lung cancer; ALK; Toxicity; Lorlatinib
• Research Categories: Health Sciences, Oncology; Health Sciences, Toxicology

Abstract

Introduction Treatment with lorlatinib for patients with advanced ALK- and ROS1-rearranged NSCLC (ALK+ and ROS1+ 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. Methods We reviewed the course of 144 patients with advanced ALK- or ROS1-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). Results 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). Conclusions 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.