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.