Comprehensive analysis of adverse event profile changes with pertuzumab addition to trastuzumab‐based breast cancer therapy: Disproportionality analysis using VigiBase

Aims: Pertuzumab is used in combination with trastuzumab-based therapy for HER2-positive breast cancer. However, real-world safety information on pertuzumab remains limited. This study assessed the safety of adding pertuzumab to trastuzumab-based therapy for HER2-positive breast cancer using real-world data.
Methods: VigiBase, the World Health Organization's global database of adverse events (AEs), containing reports from November 1967 to December 2023, was used. Signals for pertuzumab-associated AEs in breast cancer cases were detected using the reporting odds ratio (ROR).
Results: Signals of trastuzumab plus pertuzumab relative to trastuzumab alone were detected in gastrointestinal disorders (ROR: 1.45, 95% confidence interval: 1.26–1.67), including diarrhoea (3.49, 2.83–4.30); infections and infestations (1.54, 1.24–1.91); and skin and subcutaneous tissue disorders (ROR: 1.63, 1.40–1.90), including pruritus (1.96, 1.51–2.55) and rash (1.63, 1.20–2.23). Further, signals of trastuzumab plus docetaxel plus pertuzumab relative to those of trastuzumab plus docetaxel were detected in gastrointestinal disorders (1.63, 1.38–1.93), including nausea (1.72, 1.24–2.39) and vomiting (1.48, 1.01–2.17), and in nervous system disorders (1.50, 1.20–1.87), including paraesthesia (2.60, 1.33–5.08) and peripheral sensory neuropathy (5.94, 1.79–19.71). The frequency of AEs causing or prolonging hospitalization was increased with trastuzumab plus pertuzumab compared to that with trastuzumab alone (1.18, 1.00–1.38).
Conclusions: AE profiles after the addition of pertuzumab to trastuzumab-based therapy were comprehensively identified. The findings in this study highlight the importance of considering these AEs when selecting pertuzumab combination therapy to ensure the safety of patients with breast cancer.

This is the peer reviewed version of the following article: [Takeda T, Matsumoto J, Sakai T, et al. Comprehensive analysis of adverse event profile changes with pertuzumab addition to trastuzumab-based breast cancer therapy: Disproportionality analysis using VigiBase. Br J Clin Pharmacol. 2025; 1-13. doi:10.1002/bcp.70094], which has been published in final form at [https://doi.org/10.1002/bcp.70094]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

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