A Tale of Two Periods: The Evolution of Determinants and CVD Mortality Risk in Metastatic NSCLC

Immunotherapy has redefined the treatment era for metastatic non-small cell lung cancer (NSCLC); therefore, this study aimed to explore trends in survival and cardiovascular disease (CVD) mortality risk before and after the widespread adoption of immunotherapy.

This research utilized information from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and the Wide-Ranging Online Data for Epidemiologic Research (CDC-WONDER) database from the Centers for Disease Control and Prevention. The study population comprised patients with metastatic NSCLC from the pre- (2011-2014) and post-immunotherapy (2016-2019) periods. Survival determinants and CVD mortality trends were analyzed using propensity score matching, Kaplan-Meier survival analyses, competing risk models, and accelerated failure time (AFT) models.

A total of 78,028 metastatic NSCLC patients were enrolled in the study, with significant improvements noted in overall survival (OS) and cancer-specific survival (CSS) in the later stages of immunotherapy. The AFT model analysis identified treatment modality, pathological subtype, metastatic site, and some non-medical factors as survival determinants. The interaction analyses revealed that the survival differences among certain subgroups intensified in the post-immunotherapy period. Despite the lack of significant differences in CVD mortality and subgroup composition between the two periods, CVD mortality risk remained high compared with the general U.S. population.

Survival of patients with metastatic NSCLC has improved significantly since the introduction of immunotherapy. However, survival differences between some subpopulations continue to intensify, while CVD mortality risk also remains a key concern.