Association of endocrine immune-related adverse events with progression-free survival in advanced non-small cell lung cancer treated with PD-1/PD-L1 inhibitors with or without anlotinib.

Introduction: Endocrine immune-related adverse events (irAEs) are frequently observed during PD-1/PD-L1 therapy and may indicate active immune engagement during treatment. However, it remains uncertain whether this association persists in regimens incorporating anlotinib. Methods: We retrospectively analyzed 77 consecutive patients with advanced NSCLC who received PD-1/PD-L1 inhibitors plus platinum-based chemotherapy with (n = 17) or without (n = 60) anlotinib. Endocrine irAEs were defined according to the CTCAE v5.0 using assay-specific thresholds. To address the immortal-time bias, we applied prespecified 12- and 24-week landmark analyses and a time-dependent Cox model. Effect estimates were presented with 95% confidence intervals. Results: Endocrine irAEs were predominantly grades 1-2 and occurred later in patients treated with anlotinib (median onset 12 vs. 9 weeks). In the 12- and 24-week landmark analyses, where irAE status was determined at the landmark, endocrine irAEs were not significantly associated with PFS in the overall cohort (12-week HR 1.23, 95% CI 0.70-2.17; 24-week HR 1.27, 95% CI 0.67-2.43). Similarly, a time-dependent Cox model treating endocrine irAEs as time-varying covariates did not demonstrate a protective effect (HR 2.38, 95% CI 1.43-3.94). Adjusted comparisons indicated no meaningful PFS difference between treatment regimens, and the findings from the anlotinib subgroup (n = 17) were exploratory. Conclusion: In this single-center cohort, endocrine irAEs functioned as dynamic on-treatment indicators but did not confer a clear PFS advantage after bias-aware modeling. Given the limited sample size, these findings are exploratory and require further prospective validation.