Real-world effectiveness of lorlatinib in previously treated ROS1 positive NSCLC patients in Taiwan

Background: Lorlatinib is a novel ATP-competitive macrocyclic tyrosine kinase inhibitor (TKI) that targets both anaplastic lymphoma kinase (ALK) and the ROS proto-oncogene 1 (ROS1) rearrangement. ROS1 is a key driver gene found in 1 % of non-small cell lung cancers (NSCLC). Methods: This observational study analyzed the effectiveness and safety of lorlatinib in ROS1 positive advanced NSCLC patients who progressed from previous TKI therapy and subsequently received lorlatinib, regardless of chemotherapy. Patients who received lorlatinib under expanded access program in Taiwan before September 2019 were eligible. Patients were followed for at least one year from the first lorlatinib treatment until study completion. Results: Ten patients were eligible for this analysis, five males and five females, with a mean age of 47.7 years. Prior to lorlatinib treatment, four patients (40 %) had received only crizotinib, and other six (60 %) had received two or more ROS1 TKIs. The real-world overall response rate (rwORR) was 30 %, and the real-world disease control rate (rwDCR) was 90 %. The intra-cranial rwORR was 29 %, and intra-cranial rwDCR was 86 %. The overall safety profile was consistent with findings from previous clinical and real-world data studies. All patients were still alive at the end of the study. The median progression-free survival was 24.4 months (95 % confidence interval: 3.8–not reached), and 70 % of patients remained progression-free at both 12 and 18 months. Conclusion: This real-world analysis highlighted durable effectiveness of lorlatinib in treating NSCLC patients with ROS1 rearrangements in second-line and beyond settings. The safety profile aligned with previous clinical and real-world studies.