Prevalence of osimertinib-induced cardiotoxicity in non-small cell lung cancer patients: a systematic review and meta-analysis.

OBJECTIVE

Osimertinib, a third-generation Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI), is the standard of care for patients with EGFR-mutated Non-Small Cell Lung Cancer (NSCLC). While clinically effective, concerns have emerged regarding its potential cardiotoxicity. This study aims to systematically evaluate the prevalence and types of cardiotoxicity associated with Osimertinib.

METHODS

A systematic review and meta-analysis were performed in accordance with PRISMA guidelines. Literature searches of PubMed and ClinicalTrials.gov were conducted for studies published between October 2014 and October 2024. Data from 68 studies encompassing 14,050 patients were analyzed using the metafor package in R Studio (version 4.4.1). A generalized linear mixed model with logit transformation was used to estimate pooled prevalence. Heterogeneity was assessed via I statistics, and publication bias was evaluated using Egger's and Begg's tests.

RESULTS

The overall pooled prevalence of Osimertinib-induced cardiotoxicity was 4.00 % (95 % CI: 2.9-5.48; I2 = 76.9 %). QT prolongation was the most commonly reported event (6.03 %), followed by atrial fibrillation (1.50 %) and cardiac failure (1.21 %). Subgroup analysis showed higher prevalence in randomized controlled trials (4.98 %) versus observational studies (0.78 %), and in combination therapies (4.89 %) versus monotherapy (3.64 %). Regional variation was noted, with the highest prevalence in North America (5.56 %). Egger's test indicated significant publication bias (p < 0.0001) for several cardiotoxic outcomes.

CONCLUSION

Osimertinib is associated with a modest but clinically significant risk of cardiotoxicity, particularly QT prolongation. These findings support the need for routine cardiac monitoring in high-risk patients and emphasize the importance of standardized cardiotoxicity reporting in future trials to enhance the safety profile of Osimertinib in NSCLC treatment.