Advanced-stage ALK-positive non–small-cell lung cancer (NSCLC) patients: Real-world treatment patterns and outcomes from the Italian biomarker ATLAS database

BACKGROUND: Treatment of advanced ALK + NSCLC has improved with increasingly effective ALK tyrosine-kinase inhibitors (TKIs). We report real-world treatment patterns and outcomes from the Italian ATLAS registry. METHODS: Clinical-pathological and treatment data were retrospectively and prospectively collected from 37 Italian centers. RESULTS: 463 ALK + advanced NSCLC patients treated from 2019 to 2024 were included. 431 (93 %) patients received 1st line (1L) ALK TKIs, mostly alectinib (82.5 %). 1L treatment choice, reported in 142 cases, was driven by drug access as first (31 %) or subsequent lines (40.1 %) and by safety (21.8 %). Among 382 patients receiving 1L alectinib overall survival (OS) rate was 88.7 % and 73.3 % at 24 and 60 months, respectively. Median progression-free survival (mPFS) was 43.1 months (95 %CI: 29.5-57.0). Brain was a new site of progression in 11 (3.6 %) patients. Intracranial PFS rate was 73.1 % and 59.1 % at 24 and 36 months with a 64.7 % intracranial response rate. Grade ≥ 3 adverse events occurred in 41 (10.7 %) patients, mainly hepatic toxicity (13, 3.4 %) and asthenia (5, 1.3 %). At progression tissue and/or liquid biopsy were performed in 28 (23.5 %) and 20 (16.8 %) cases, respectively. Out of 80 patients receiving 2nd line therapy after alectinib, 67 (83.8 %) received lorlatinib achieving mPFS 7.5 (95 % CI: 6.2-8.8) and mOS 26.4 months (95 % CI: 19.1-33.7). 17 (15.5 %) patients died without second line therapy. CONCLUSIONS: Real-world data confirm the effectiveness and safety of alectinib, used as preferred upfront ALK-TKI. The recent 1L lorlatinib approval might change this scenario. Tissue/liquid biopsy at disease progression are underperformed in clinical practice.