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

BackgroundTreatment of advanced ALK+ NSCLC is rapidly improving with the approval of several ALK tyrosine-kinase inhibitors (TKIs) of growing efficacy. Here we report treatment patterns and outcomes from the Italian real-world registry ATLAS.MethodsClinical-pathological features, treatment effectiveness and safety were retrospectively collected from the ATLAS registry.ResultsData of 463 ALK+ advanced NSCLC patients from July 2019 to March 2024 across 37 Italian centers were analyzed. Median age was 61 years; mostly females (264;57%), with adenocarcinoma histology (447;96.5%). 121(26.1%) had baseline brain metastases. 431(93%) patients were treated with 1st line ALK TKI, mostly with Alectinib (82.5%). Factors driving 1st line treatment choice were reported in 142 cases and were mainly related to drug access as first (31%) or subsequent lines (40.1%) according to regulatory indications, and safety profile (21.8%). Among the 382 patients receiving 1st line alectinib, overall survival (OS) rate was 88.7% and 73.3% at 24 and 60 months (mo), respectively. Median progression-free survival (mPFS) was 43.1 mo (95%CI: 29.5-57.0). 11 patients out of 306 (3.6%) had brain as a new site of progression. Among the 77 patients with baseline brain metastases intracranial PFS rate was 73.1% and 59.1% at 24 and 36 mo, respectively, with intracranial response rate of 64.7%. 41(10.7%) patients had grade≥3 adverse events, mostly hepatic toxicity (13, 3.4%) and asthenia (5, 1.3%). At disease progression tissue rebiopsy was performed in 28(23.5%) and liquid biopsy in 20(16.8%) cases; ALK G1202R was the most frequent mechanism of resistance identified (11%). Out of 80 patients receiving 2nd line therapy after alectinib failure, 67 (83.8%) received lorlatinib achieving a mPFS of 7.5 (95% CI: 6.2-8.8) and mOS of 26.4 mo (95% CI: 19.1-33.7).ConclusionsReal-world data confirm the effectiveness and safety of alectinib, used as preferred upfront ALK-TKI. The recent 1st line lorlatinib approval might change this scenario. Tissue or liquid biopsy at the time of progression are underperformed in clinical practice, highlighting the need of a raising awareness on the importance of resistance mechanisms identification.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.