OBJECTIVES: Immuno-oncology therapies (I-O) have significantly changed the treatment approach for non-small cell lung cancer (NSCLC). This study aims to assess mortality rates, their causes, and associated risk factors in patients with NSCLC before and after the introduction of I-O.

METHODS: This retrospective cohort study used the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare linked database from 2006 to 2019. We identified older patients (aged 65 years or older) diagnosed with advanced NSCLC in two periods: January 2013 to September 2015 (pre–I-O) and October 2015 to December 2017 (post–I-O). The outcomes were all-cause and cause-specific mortality, classified as cardiovascular disease (CVD), NSCLC, and others. The multivariate Cox regression model estimated adjusted hazard ratios for all-cause mortality, and the Fine-Gray model for NSCLC and CVD mortality. We included demographics, tumor characteristics, and comorbidities to examine their association with mortality.

RESULTS: Among 52,015 older patients with NSCLC, 30,257 (58.17%) and 21,758 (41.83%) identified pre– and post–I-O, respectively. The majority of patients died from NSCLC (pre–I-O: 59.87%; post–I-O: 55.24%). In post–I-O, the risk of all-cause mortality was significantly reduced (hazard ratio (HR)=0.88; 95% confidence interval (CI): 0.87-0.90). Significant risk factors for all-cause mortality included race, low-income level, history of alcohol use, and comorbidities such as peripheral vascular disease. Regarding cause-specific mortality, post–I-O patients had a lower risk of CVD mortality (sub-distribution HR (sHR)=0.75; 95% CI: 0.67-0.84) and NSCLC mortality (sHR=0.77; 95% CI: 0.75-0.79) compared to pre–I-O. The risk of CVD death was higher among Blacks compared to Whites (sHR=1.52; 95% CI: 1.28-1.81).

CONCLUSIONS: We found that I-O therapy decreased the risk of overall, NSCLC-caused, and CVD-caused mortality among older patients with advanced NSCLC and that comorbidities and socioeconomic status were predictors of mortality.