Impact of the immuno-oncology era on cerebrovascular disease and cancer-specific mortality in older adults with advanced non-small cell lung cancer: a competing-risks cohort study.

Background: Immune checkpoint inhibitors (ICIs) have substantially improved survival for patients with advanced non-small cell lung cancer (NSCLC). However, among older adults, improved cancer survival may be accompanied by shifts in competing causes of death, including cerebrovascular disease (CVD). Population-level evidence describing how the introduction of immuno-oncology (I-O) has influenced cause-specific mortality in older patients with advanced NSCLC remains limited. Methods: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from 2007 to 2022. Patients aged ≥70 years with advanced NSCLC were classified into a preimmuno-oncology era (Pre-I-O; 2007-2014) and a post-immuno-oncology era (Post-I-O; 2015-2022) based on diagnosis date. Propensity score matching (PSM) (1:1) was applied to balance demographic, socioeconomic, tumor, and treatment characteristics. Death outcomes included CVD death, NSCLC-specific death, and other-cause death. Cumulative incidence functions were estimated, and Fine-Gray competing-risks models were used for primary analyses. Cause-specific Cox regression and multistate models were conducted as sensitivity analyses. Subgroup analyses assessed consistency across clinically relevant strata. Results: After PSM, 37,169 patients were included in each era. Cumulative incidence analyses demonstrated lower NSCLC-specific mortality but higher CVD mortality in the Post-I-O. In Fine-Gray competing-risks models, Post-I-O diagnosis was associated with a significantly reduced sub-distribution hazard of NSCLC-specific death [sub-distribution hazard ratio (sHR) 0.624, 95% confidence interval (CI): 0.613-0.635; P<0.001] and an increased sub-distribution hazard of CVD death (sHR =1.424, 95% CI: 1.293-1.657; P<0.001). Cause-specific Cox models yielded consistent findings for NSCLC death [hazard ratio (HR) =0.739, 95% CI: 0.727-0.752] and CVD death (HR =1.425, 95% CI: 1.217-1.699). Multistate modeling further supported a lower overall mortality hazard in the Post-I-O (HR =0.746, 95% CI: 0.735-0.758). Subgroup analyses demonstrated generally consistent associations across age, sex, race, and treatment strata. Conclusions: Among adults aged ≥70 years with advanced NSCLC, the I-O era was associated with substantially lower cancer-specific mortality but higher CVD mortality. These findings highlight the growing importance of cerebrovascular risk assessment and integrated survivorship care as cancer outcomes improve in older populations.