Multicenter phase 2 trial of lorlatinib in TKI-naïve advanced ROS1-positive non-small cell lung cancer

Lorlatinib is a third-generation tyrosine kinase inhibitor (TKI) targeting ROS1 and ALK. A multicenter phase 2 nonrandomized clinical trial in South Korea evaluated lorlatinib for advanced ROS1-positive non-small cell lung cancer in TKI-naïve patients with an ECOG performance status of 2 or less, after one or no prior line of platinum-based chemotherapy. Patients received lorlatinib 100 mg once daily until disease progression or unacceptable toxicity. The study included 32 patients (mean age 59 ± 11 years; 63% females; 21 treatment-naïve and 11 after prior chemotherapy). The median duration of follow-up was 22.1 months. The primary endpoint was objective response rate. The ORR was 73% (95% CI 56-86) and the disease control rate was 90% (74-97). Median progression-free survival was 53.6 months (95% CI 27.8-79.5) and the median overall survival was not reached. For treatment-naïve versus previously treated patient, the ORR was 90% versus 60%, and PFS was not reached versus 35.8 months. Grade 3 or 4 hypertriglyceridemia occurred in 16% of patients and grade 3 0r 4 hypercholesterolemia in 25%. No treatment-related deaths occurred. The authors conclude that lorlatinib demonstrated durable efficacy and manageable safety in TKI-naïve advanced ROS1-positive NSCLC.