Reconciling Conflicting Evidence on Peri-Immune Checkpoint Inhibitor COVID-19 mRNA Vaccination in Lung Cancer: A Time-Aligned Target Trial Emulation-Informed Landmark Study.
Recent reports suggest that peri-immune checkpoint inhibitor (ICI) COVID-19 mRNA vaccination may improve survival in lung cancer, but time-related and calendar-time biases may inflate real-world estimates. We evaluated vaccination timing and outcomes using a target trial emulation-informed, time-aligned design.
This retrospective cohort study used deidentified electronic health record data from the TriNetX Global Collaborative Network. Time zero was first ICI administration. New users initiating ICI therapy from September 2, 2020, through December 31, 2025, were classified by mRNA vaccination within -100 to +100 days as peri-ICI, pre-only, post-only, or none. Follow-up began at a prespecified day-100 landmark. Cohorts were balanced using 1:1 propensity score matching. Endpoints were overall survival (OS) and time to next systemic treatment or death (TTNT-D).
After matching, 2,286 patients were included per group (4,572 total). Peri-ICI mRNA vaccination was not associated with OS (hazard ratio [HR] 1.005, 95% confidence interval [CI] 0.913-1.106) or TTNT-D (HR 1.059, 95% CI 0.956-1.174). The pre-only versus post-only OS estimate was near null (HR 0.920, 95% CI 0.804-1.053), with concordant patterns across prespecified sensitivity analyses.
Peri-ICI COVID-19 mRNA vaccination was not associated with improved outcomes in patients with lung cancer. These findings clarify discrepant reports and underscore the importance of rigorous time alignment when evaluating time-dependent exposures.
This retrospective cohort study used deidentified electronic health record data from the TriNetX Global Collaborative Network. Time zero was first ICI administration. New users initiating ICI therapy from September 2, 2020, through December 31, 2025, were classified by mRNA vaccination within -100 to +100 days as peri-ICI, pre-only, post-only, or none. Follow-up began at a prespecified day-100 landmark. Cohorts were balanced using 1:1 propensity score matching. Endpoints were overall survival (OS) and time to next systemic treatment or death (TTNT-D).
After matching, 2,286 patients were included per group (4,572 total). Peri-ICI mRNA vaccination was not associated with OS (hazard ratio [HR] 1.005, 95% confidence interval [CI] 0.913-1.106) or TTNT-D (HR 1.059, 95% CI 0.956-1.174). The pre-only versus post-only OS estimate was near null (HR 0.920, 95% CI 0.804-1.053), with concordant patterns across prespecified sensitivity analyses.
Peri-ICI COVID-19 mRNA vaccination was not associated with improved outcomes in patients with lung cancer. These findings clarify discrepant reports and underscore the importance of rigorous time alignment when evaluating time-dependent exposures.