BRIEF RESEARCH REPORT article
Front. Oncol.
Sec. Thoracic Oncology
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
Furong Sun 1
Yuzhu Gao 2
Xiaoyan Zheng 1
Jie Hua 1
Shouzhen Liu 1
Dong Cao 2
Jianping Zhou 3,4
1. Department of Respiratory and Critical Care Medicine, Zhoushan Branch, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Zhoushan, China
2. School of Medical Information Engineering, Guangzhou University of Chinese Medicine, Guangzhou, China
3. Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital Department of Pulmonary and Critical Care Medicine, Shanghai, China
4. Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Abstract
Introduction: Endocrine immune-related adverse events (irAEs) are frequently observed during PD-1/PD-L1 therapy and may indicate active on-treatment immune engagement. Whether this association persists in regimens incorporating anlotinib remains uncertain. Methods: We retrospectively analyzed 77 consecutive patients with advanced NSCLC who received PD-1/PD-L1 inhibitors plus platinum chemotherapy with (n = 17) or without (n = 60) anlotinib. Endocrine irAEs were defined according to CTCAE v5.0 using assay-specific thresholds. To address immortal-time bias, we applied prespecified 12 and 24 week landmark analyses and a time-dependent Cox model. Effect estimates are presented with 95% confidence intervals. Results: Endocrine irAEs were predominantly grade 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 a time-varying covariate 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; findings from the anlotinib subgroup (n = 17) were exploratory. Sun et al. Endocrine irAEs and PFS in NSCLC 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 prospective validation.
Summary
Keywords
Anlotinib, endocrine immune-related adverse events, non-small-cell lung cancer, PD-1/PD-L1 inhibitors, progression-freesurvival
Received
09 September 2025
Accepted
03 February 2026
Copyright
© 2026 Sun, Gao, Zheng, Hua, Liu, Cao and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Dong Cao; Jianping Zhou
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