Fusion-positive early-stage and locally advanced lung cancers: A real-world analysis of event-free, disease-free, and overall survival.

8036 Background: Fusion-positive lung cancers are a distinct subset of lung cancers. While outcomes in metastatic disease are comprehensively characterized, data on survival and disease recurrence outcomes after definitive therapy in non-metastatic disease remain limited. Methods: This was a single institution, retrospective study, including patients (pts) with ALK/ROS1/RET/NTRK+ early-stage/locally advanced lung cancer pts diagnosed between 2012-2025. The primary endpoint in pts who underwent curative surgery or stereotactic body radiotherapy (SBRT) was disease-free survival (DFS; time from curative therapy to disease recurrence or death). The primary endpoint in pts initially treated with neoadjuvant therapy prior to surgery or definitive chemoradiation was event-free survival (EFS; time from curative therapy to disease progression, recurrence, failure of treatment or death). Overall survival (OS) from the start of curative therapy was analyzed. Results: 179 pts (82 ALK , 38 ROS1 , 55 RET , 4 NTRK ) were identified. Median EFS across all pts for ALK/ROS1/RET/NTRK was 4.4yrs (95%CI: 2.8, Not Reached (NR)), 3.4yrs (95%CI: 2.0, NR), 7.4yrs (95%CI: 4.6, NR) and 3.0yrs (95%CI: 0.4, NR), respectively. Median OS for ALK/ROS1/RET/NTRK pts was: 13.0yrs (95%CI: 12.0, NR), 12.0yrs (95%CI: 11.0, NR), 14.0yrs (95%CI: 12.0, NR) and NR (95%CI: 5.4, NR), respectively. 132/179 (74%) of all pts were treated with surgery (128 pts) or SBRT (4 pts) first. Median EFS for pts treated with neoadjuvant treatment first (N=26) for ALK (n=15) /ROS1 (n=5) /RET (n=6) pts was 0.9yrs (95%CI: 0.8, NR), 0.9yrs (95%CI: 0.7, NR) and NR (95%CI: 0.2, NR), respectively. Median EFS for pts treated with chemoradiation first (N=21) for ALK (n=7) /ROS1 (n=5) /RET (n=9) pts was NR (95%CI: 0.5, NR), 0.6yrs (95%CI: 0.5, NR) and 1.0yrs (95%CI: 0.8, NR), respectively. Median DFS for pts treated with surgery/SBRT first (N=132) for ALK (n=60) /ROS1 (n=28) /RET (n=40) /NTRK (n=4) pts was: 5.1yrs (95%CI: 3.8, NR), 5.2yrs (95%CI: 3.2, NR), NR (95%CI: 6.6, NR) and 3.0yrs (95%CI: 0.4, NR), respectively. Conclusions: This is the largest series on outcomes in fusion-positive early stage/locally advanced lung cancers treated with definitive therapy. Prolonged EFS, DFS, and OS were observed.