Real-life efficacy and safety data of lorlatinib treatment in ROS-1–positive advanced non-small cell lung cancer: Turkish Oncology Group (TOG) study.

e20659 Background: ROS-1-positive non-small cell lung cancers (NSCLCs) are rare, accounting for approximately 1-2% of all NSCLCs. Lorlatinib is a potent, third-generation tyrosine kinase inhibitor targeting ALK and ROS1 with preclinical activity against most of the known resistance mutations in ALK and ROS1, with good cranial efficacy. Lorlatinib has shown clinical activity in patients with advanced ROS1-positive NSCLC, including those with CNS metastases and those previously treated with crizotinib, in phase 1 to 2 clinical trials. We aimed to present real-life data on the efficacy and safety of lorlatinib in ROS-1 positive NSCLC patients. Methods: Our study is a retrospective study and ROS-1 positive patients with NGS or FISH techniques among non-small cell lung cancer patients between 2014 and 2024 were included in the study. A total of 52 patients from twenty oncology centers were eligible for the study. Median progression-free survival (mPFS) and overall survival (mOS) were estimated by analyzing the Kaplan-Meier curve. Results: Median age of patients was 52 years. 33 (63.5%) of our patients were male, and 23 (44%) had never smoked. 49 (94%) patients had adenocarcinoma histology. At the time of diagnosis, 48 (92%) of the patients were metastatic and 12 (23%) had brain metastases. In first-line 39 (75%) patients received crizotinib and in second-line 41 (78%) patients were treated with lorlatinib. At least 3 or more metastatic sites were present in 37 (71%) patients before lorlatinib treatment. Median follow-up was 20.4 months and mPFS with lorlatinib treatment was 27.2 months. Side effects were observed in 38 (73%) patients with lorlatinib, and 10 (19%) had grade 3-4-5 side effects. The most common grade 3-4 side effect was hyperlipidemia, which was seen in 4 (7.7) of the patients. Dose reduction was performed in 10 (19%) patients due to side effects and treatment was interrupted in 8 (15%) of them. Treatment was not discontinued in any patient due to side effects. Conclusions: In summary, lorlatinib showed clinical activity in patients with advanced ROS1-positive NSCLC. Lorlatinib has side effects and these side effects are manageable. There are few treatment options for patients who progress under crizotinib therapy, lorlatinib can be used safely and effectively as a next-line targeted agent.