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. 2025 Feb 24:15:1528950.
doi: 10.3389/fonc.2025.1528950. eCollection 2025.

Cardiovascular toxicity induced by immunotherapy in non-small cell lung cancer: a systematic review and meta-analysis of observational studies

Josep Sabaté-Ortega  1   2 , Eduard Teixidor-Vilà  1   2 , Èlia Sais  1   2   3 , Alejandro Hernandez-Martínez  1   2 , Claudia Montañés-Ferrer  1   2 , Núria Coma  4 , Emma Polonio-Alcalá  2 , Victor Pineda  5 , Joaquim Bosch-Barrera  1   2   3
Affiliations

Cardiovascular toxicity induced by immunotherapy in non-small cell lung cancer: a systematic review and meta-analysis of observational studies

Josep Sabaté-Ortega et al. Front Oncol. .

Abstract

Background: Immune checkpoint inhibitors (ICIs), an immunotherapy used in cancer treatment, are associated with potential cardiovascular (CV) toxicity. Monitoring CV issues in non-small cell lung cancer (NSCLC) patients is challenging due to their lower incidence and diversity. Hence, enhancing our understanding of CV toxicities in patients receiving ICIs is required to improve their quality of life and survival. Hence, the main objective of this study is the evaluation of CV side effects in ICI-treated NSCLC patients by assessing the prevalence and hazard of CV events.

Methods: A systematic review was conducted to identify relevant studies, up to November 21st, 2023. A meta-analysis was performed to examine the data extracted from the selected studies. The random-effects model was applied to account for heterogeneity among studies, reporting results as prevalence rates and hazard ratios (HR) alongside their corresponding 95% confidence intervals (CI). Studies meeting inclusion criteria were selected and outcomes were assessed through qualitative analysis.

Results: Twelve observational studies using Real world Data were included, encompassing 23,621 patients with NSCLC. Our findings indicated that patients treated with ICIs exhibited a 3% prevalence of CV events and a significantly higher hazard (HR = 1.78 (95% CI: 1.46, 2.17); p < 0.00001; I2 = 72%) compared to patients treated with other drugs.

Conclusions: The treatment with ICIs caused a higher rate of CV events compared to non-ICI treatments. Nevertheless, further research is required to elucidate the underlying mechanisms and implications for patient care. This calls for continued research efforts to optimize the cardiovascular health of patients undergoing immunotherapy for lung cancer.

Keywords: cardiovascular events; immune checkpoint inhibitors; immunotherapy; lung cancer; prevalence.

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Conflict of interest statement

ET-V has received support for attending meetings and/or travel from Lilly, Roche, and MSD. AHM received support for attending meetings from BMS and Lilly. JB-B reports personal fees from MSD, BMS, AstraZeneca, and Sanofi, outside the submitted work and has received support for attending meetings and/or travel from Takeda, MSD, and Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
The stepwise process from initial study identification, screening, determination of eligibility, and final study inclusion, as illustrated in the PRISMA flow chart of included and excluded studies, resulted in the selection of twelve observational studies.
Figure 2
Figure 2
Funnel plot illustrating cardiovascular side effects in immune checkpoint Inhibitor-treated patients across included studies.
Figure 3
Figure 3
Forest Plot illustrating the prevalence of cardiovascular events in patients with lung cancer treated with immune checkpoint inhibitors.
Figure 4
Figure 4
Forest Plot illustrating the hazard ratio in patients with lung cancer treated with immune checkpoint inhibitors.
See this image and copyright information in PMC

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