Treatment duration of immune checkpoint inhibitors and overall survival in U.S. veterans with Cancer

BackgroundOptimal treatment duration for immune checkpoint inhibitors (ICI) remains a clinical debate. The objective of this study was to contrast mortality rates between 2-year fixed versus indefinite treatment duration among patients initiating ICIs across a variety cancer types.MethodsThis retrospective observational study used national administrative data from the Veterans Health Administration to select patients who initiated an ICI between January 1, 2014, and December 31, 2020. ICI treatment duration was categorized as either fixed (2 years; 700-760 days) or indefinite (>760 days). A multivariate Cox proportional hazards regression model was used to examine the impact of duration on overall mortality.ResultsOf 1357 patients who received ICI treatment for at least 2 years, the probability of survival after 1 year was significantly lower in the fixed duration group (78.9%) compared to the indefinite duration group (87.6%; χ² = 12.6; df = 1; p < 0.001). At 2 years follow-up overall survival was not significantly different between groups (70.9% fixed vs. 76.5% indefinite; χ² = 3.5; df = 1; p = 0.061). In a multivariable Cox proportional hazards regression model, the adjusted HR for death for fixed versus indefinite duration groups was 1.22 (95% CI: 0.96-1.54), which did not reach statistical significance.ConclusionWhile failing to demonstrate a statistically significant difference, these findings suggest the potential for a clinically meaningful difference in mortality risk between fixed versus indefinite duration ICI treatment. These findings support the need for further research to determine the optimal duration for ICI treatment, and highlight weighing risks of mortality, immune-related adverse events, and financial cost.