OBJECTIVES: Despite growing concerns regarding the cardiovascular safety of Programmed Cell Death Protein 1 (PD-1) inhibitors, especially nivolumab and pembrolizumab, little is known about the factors associated with cardiovascular disease (CVD) mortality in patients with non-small cell lung cancer (NSCLC). This study examines the competing risks of the cause of death (CoD) among older patients with NSCLC receiving PD-1 inhibitors and identifies factors influencing CVD and NSCLC mortality.

METHODS: This retrospective cohort study used the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare linked database from 2006 to 2019. We identified older adults (aged 65 years or older) diagnosed with advanced NSCLC who used pembrolizumab or nivolumab between 2007 and 2017. The outcomes included four types of mortality: CVD, NSCLC, other cancers, and other diseases. The predictors included age, sex, stage, socioeconomic status, and comorbidities. The Fine-Gray model and the cause-specific Cox regression model were used to assess CVD or NSCLC mortality and associated factors.

RESULTS: Among 6,688 patients, 67.57% (n=4,519) were treated with nivolumab, and 32.43% (n=2,169) with pembrolizumab. Among patients who died (n=4,841), the majority died from NSCLC (84.67%), and CVD deaths accounted for 3.12% (nivolumab: 2.81%; pembrolizumab: 3.98%). CVD mortality risk was not significantly different between the two PD-1 inhibitors (sub-distribution HR (sHR)=1.08; 95% CI: 0.74-1.59; cause-specific HR=1.39; 95% CI: 0.90-2.14). A history of heart failure increased the risk of CVD death (sHR=2.39; 95% CI: 1.70-3.35), while non-Medicaid status was associated with a lower CVD death compared to having Medicaid (sHR=0.69; 95% CI: 0.53-0.90). NSCLC mortality was higher in Stage IV/distant than Stage IIIB/regional (sHR=1.25; 95% CI: 1.16-1.36) and s lower in females (sHR=0.87; 95% CI: 0.82-0.93).

CONCLUSIONS: Among older patients with advanced NSCLC, Medicaid dual eligibility, and a history of heart failure are risk factors for CVD death, while a higher stage and male gender are risk factors for NSCLC death.