Introduction: Non-small-cell lung cancer (NSCLC) patients harboring ALK or ROS1 rearrangements invariably acquire resistance to the first- and second-generation tyrosine kinase inhibitors (TKIs), most notably ALK G1202R and ROS1 G2032R. Lorlatinib, a novel third-generation TKI, produced remarkable results from the first-in-man phase 1 trial: an overall response rate of 46% and 50% for previously treated ALK- and ROS1-positive patients, respectively. However, the efficacy of lorlatinib has not been widely validated in Asian patients.
Patients and methods: Patients with advanced NSCLC with ALK or ROS1 rearrangements who initiated lorlatinib therapy between November 2016 and July 2018 were retrospectively analyzed.
Results: Twelve consecutive patients were included. The median age was 55 years (range, 36-76 years). Ten (83%) had ALK-positive NSCLC and 2 (17%) had ROS1-positive NSCLC. All patients had a history of first- or second-generation ALK TKI receipt. Two ALK-positive patients and one ROS1-positive patient had the G1202R and G2032R mutations, respectively. The overall response rate was 64% and the disease control rate was 91%. Of the 3 ALK-positive patients with intracranial target lesions, 1 (33%) had a complete response and 2 (67%) a partial response, producing an intracranial objective response of 100%. The median progression-free survival was 6.5 months (range, 1.0-16.5 months). The most common adverse event was hypercholesterolemia (83%), and no adverse event-related dose reductions or treatment discontinuations were reported.
Conclusion: This study is the first to report that lorlatinib is an important novel therapeutic option for Asian patients who have advanced NSCLC harboring ALK/ROS1 mutations whose disease progressed during treatment with first- and second-generation TKIs.
Keywords: Asian; PF-06463922.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.