1283P - Advanced 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 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.

Methods

Clinical-pathological features, treatment effectiveness and safety were retrospectively collected from the ATLAS registry.

Results

Data 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 1^st line ALK TKI, mostly with Alectinib (82.5%). Factors driving 1^st 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 1^st 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 2^nd 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).

Conclusions

Real-world data confirm the effectiveness and safety of alectinib, used as preferred upfront ALK-TKI. The recent 1^st 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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.