How immune-related adverse events differ in elderly gastrointestinal vs. lung cancer patients

With global aging, lung and gastrointestinal (GI) cancers are leading malignancies among elderly populations, with 681,124 and 333,821 new cases in elderly Chinese patients in 2024, respectively. Immune checkpoint inhibitors (ICIs) have become a cornerstone of treatment, offering better tolerability than chemotherapy in elderly patients. However, elderly patients are underrepresented in clinical trials, and tumor-specific differences in ICI-related immune-related adverse events (irAEs) remain unclear—posing challenges to personalized treatment decisions.

To address this gap, a retrospective real-world study led by Peking University Cancer Hospital enrolled 407 elderly patients (≥ 70 years) who received ≥ 2 cycles of ICIs between January 2016 and February 2022, including 261 with GI tumors and 146 with lung cancer. A 2:1 propensity score matching (PSM) was used to balance baseline characteristics (sex, smoking history, Eastern Cooperative Oncology Group score, combined therapies, etc.), resulting in 197 patients in the GI cohort and 133 in the lung cancer cohort. IrAEs were evaluated using Common Terminology Criteria for Adverse Events version 4.03, with the primary endpoint of any-grade irAE incidence and the secondary endpoint of organ-specific toxicity differences. The study was published online in Chinese Medical Journal on April 03, 2026.

Key findings revealed that the overall incidence of any-grade irAEs was 52.6%, with a significantly higher rate in lung cancer patients (61.0%) than in GI tumor patients (47.9%, P = 0.013). After PSM, lung cancer patients still showed a trend toward higher irAE incidence (61.7% vs. 50.8%, P = 0.056), with more grade 1-2 irAEs (52.6% vs. 37.1%, P = 0.006). Organ-specific differences were notable: skin toxicity was the most common irAE (23.8%) and more frequent in GI tumor patients (28.7% vs. 15.1%, P = 0.002), while thyroid dysfunction (17.7% overall) was more prevalent in lung cancer patients (28.1% vs. 11.9%, P < 0.001). No significant differences were observed in other irAEs (e.g., hepatotoxicity, cytopenia, pneumonitis).

This study is the first large-scale real-world analysis of tumor-specific irAEs in elderly cancer patients, providing critical evidence for clinical practice: enhanced monitoring of overall irAEs (especially thyroid dysfunction) in elderly lung cancer patients, and vigilance for skin toxicity in GI tumor patients. Mechanistically, differences may be linked to tumor microenvironment heterogeneity and gut microbiota dysbiosis. Limitations include a single-center design and a lack of data on irAE-efficacy correlations, highlighting the need for multicenter studies to validate findings.

Reference 

DOI: https://doi.org/10.1097/CM9.0000000000004069

About Yuyan Wang from Peking University Cancer Hospital

Yuyan Wang, MD, PhD, is a Chief Physician and Associate Professor in the Department of Thoracic Oncology, Peking University Cancer Hospital. She has nearly 20 years of experience in thoracic oncology, focusing on standardized and multidisciplinary treatment of lung cancer, pleural mesothelioma, and thymoma. Her research interests include molecular targeted drug resistance mechanisms and tumor metastasis microenvironment. She has led multiple national and provincial projects, published numerous SCI papers in journals such as Nat. Commun and Cancer Lett., and won several academic awards.

Funding information

This study was supported by a grant from Peking University Cancer Hospital, Grant No. JC202309; the Clinical Research Fund For Distinguished Young Scholars of Peking University Cancer Hospital (QNJJ202213); and the Health Research Exchange Program in the Health Field (Young and Middle-aged Lung Cancer Expert Research Project) (No. 1-16).