BIOM-11. THROMBOEMBOLIC RISK STRATIFICATION BY KRAS, ALK, EGFR, AND PD-L1 STATUS IN IMMUNOTHERAPY-TREATED NON-SMALL CELL LUNG CANCER WITH BRAIN METASTASES

Abstract Non-small cell lung cancer (NSCLC) with oncogenic driver mutations has a high predilection toward brain metastases (BM) and is a significant cause of morbidity and mortality worldwide. While these molecular subtypes are well-characterized for their central nervous system involvement, their impact on thromboembolic risk remains unclear. Understanding this relationship may help guide risk stratification models and anticoagulation strategies for NSCLC-BM patients. In this retrospective study, a cohort of 94 NSCLC-BM patients who received immunotherapy at any time during their disease were stratified by mutation status: PD-L1, KRAS, EGFR, and ALK. Clinically significant thrombosis (CST), comprising ischemic stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI), was calculated for each subgroup and chi-squared bivariate analysis assessed associations between mutation status (positive vs negative) and thromboembolic risk. Of 94 patients, 58 (61.7%) had at least one mutation. Many showed overlap, with 48 PD-L1(+), 26 KRAS(+), 33 EGFR(+), and 31 ALK(+). CST occurred in 28/58 cases (8 stroke, 9 DVT, 6 PE, 5 MI). KRAS(+) showed significantly reduced DVT, PE, and MI risk (p<0.05). ALK(+) also showed significantly lower DVT risk (p=0.037) and trended toward reduced stroke, PE, and MI. EGFR-positivity showed a non-significant increase in stroke but trended toward reduced rates of other thromboembolic events. PD-L1(+) status showed no significant associations but trended toward increased stroke risk (p=0.104). These findings suggest that oncogenic driver mutations in NSCLC-BM are associated with varying thromboembolic risks, with KRAS- and ALK-positivity showing a significantly reduced risk of CST which may reflect protective effects of targeted therapies. Given high mutational co-occurrence, further studies are needed to assess the impact of targeted therapies on thromboembolic events across different molecular subtypes to enable more precise risk stratification and inform more personalized treatment strategies.