With global ageing, 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 tumour-specific differences in ICI-related immune-related adverse events (irAEs) remain unclear—posing challenges to personalised 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 tumours 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.

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 tumour 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 tumour 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 tumour-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 tumour patients.

Mechanistically, differences may be linked to tumour microenvironment heterogeneity and gut microbiota dysbiosis.

Limitations include a single-centre design and a lack of data on irAE-efficacy correlations, highlighting the need for multicenter studies to validate findings.

Source: Chinese Medical Journals Publishing House Co., Ltd.