Long-Term Outcomes and Prognostic Factors in Metastatic ALK-Rearranged Non-Small Cell Lung Cancer Treated with ALK Tyrosine Kinase Inhibitors: Real-World Evidence from a High-Volume Thoracic Diseases Center.

Background/Objectives: ALK tyrosine kinase inhibitors (TKIs) have improved outcomes in patients with metastatic ALK-rearranged non-small cell lung cancer (NSCLC). However, real-world data on long-term outcomes, prognostic factors, and treatment sequencing remain limited. This study aimed to evaluate treatment outcomes, prognostic factors, and lorlatinib efficacy in different treatment settings. Methods: We retrospectively analyzed 83 patients with metastatic ALK-rearranged NSCLC treated with ALK TKIs at a tertiary oncology center. Survival outcomes, prognostic factors, treatment sequences, and adverse events were analyzed using Kaplan-Meier and Cox regression methods. Results: The median follow-up duration was 69.4 months, and the median overall survival (OS) was 73.9 months (95% CI, 58.51-89.32). Median OS was 84.8 months with first-line alectinib and 63.6 months with crizotinib. Median progression-free survival (PFS) durations were 47.5, 23.0, and 14.9 months for alectinib, brigatinib, and crizotinib, respectively. ECOG performance status, histological subtype (adenocarcinoma vs. non-adenocarcinoma), and PD-L1 expression were significant prognostic factors. First-line lorlatinib demonstrated durable disease control, with median PFS not reached and a 24-month PFS rate of 80%. Later-line lorlatinib showed continued activity, with median PFS-2 and PFS-3 of 12.2 and 6.1 months, respectively. Treatment-related adverse events were generally manageable. Conclusions: This real-world study provides long-term outcomes and prognostic insights in metastatic ALK-rearranged NSCLC. ECOG performance status, histological subtype, and PD-L1 expression were independent prognostic factors for OS. First-line lorlatinib findings suggest durable disease control but remain preliminary and require confirmation with longer follow-up.