Cardiovascular and cancer-specific mortality in older patients with advanced non-small cell lung cancer following the introduction of immuno-oncology therapies

Introduction Immuno-oncology (I-O) therapies have significantly improved survival outcomes in patients with non-small cell lung cancer (NSCLC). However, older patients, who account for a substantial proportion of NSCLC cases, are frequently underrepresented in clinical trials. The complexities of aging and associated comorbidities highlight the need for tailored treatment strategies in this population. This study aimed to evaluate mortality patterns and causes of death among older patients with advanced NSCLC before and after the introduction of I-O therapies in the United States, while also investigating factors associated with competing risks of NSCLC-specific and other cause-specific deaths in both periods. Materials and Methods We conducted a retrospective cohort study using the 2012–2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients aged 65 years or older with advanced NSCLC were included and classified into two cohorts based on their diagnosis date: pre–I-O (January 2013 – February 2015) and post–I-O (March 2015 – December 2017). Mortality outcomes included deaths from cardiovascular disease (CVD), NSCLC, and other causes. Predictors included sociodemographic factors (e.g., race, income level) and clinical factors (e.g., histology, surgery history, comorbidities). Competing risk analyses were conducted using the Fine-Gray model, while the cause-specific Cox model was employed for sensitivity analysis. Results Among 51,612 patients (51 % male; mean age: 77 years), more than half of all deaths were attributed to NSCLC (pre–I-O: 60.32 %; post–I-O: 55.96 %). After adjusting for covariates, mortality from CVD (sub-distribution hazard ratio [sHR] = 0.81; 95 % CI: 0.72–0.90) and NSCLC (sHR = 0.80; 95 % CI: 0.79–0.82) declined in the post–I-O period compared to the pre–I-O period. Comorbidities related to CVD, including peripheral vascular disease (sHR = 1.52 in pre–I-O; sHR = 1.47 in post–I-O) and cerebrovascular disease (sHR = 1.47 in pre–I-O; sHR = 1.44 in post–I-O) were associated with significantly increased CVD mortality in both periods. Discussion This study identified significant reductions in CVD- and NSCLC-related mortality during the post-IO period compared to the pre-IO period among older patients with advanced NSCLC. However, despite these improvements, our findings underscore the continued need to manage comorbidities and address socioeconomic disparities to optimize outcomes in geriatric oncology.