Real-World Cardiotoxicity of Biosimilar versus Reference Trastuzumab in Early HER2-Positive Breast Cancer

Trastuzumab has greatly improved outcomes in patients with human epidermal growth factor receptor 2-positive breast cancer. To reduce costs and increase access, biosimilar products were approved after trials demonstrated short-term safety similar to that of reference trastuzumab. However, real-world data on cardiac safety are limited.

We evaluated the adoption of biosimilar trastuzumab and compared heart failure (HF) risk between users of reference and biosimilar trastuzumab.

Patients aged ≥18 years with breast cancer who received trastuzumab from 2018 to 2024 were identified in the IQVIA PharMetrics Plus Closed Health Plan Claims database. Patients who underwent surgery within the first year after cancer diagnosis were selected as a proxy for early-stage disease. Healthcare Common Procedure Coding System Level II codes were used to identify reference and biosimilar trastuzumab use, and International Classification of Diseases codes were used to identify HF diagnoses. Patients with an HF diagnosis before breast cancer surgery were excluded. Multivariable cause-specific Cox proportional hazards regression was used to examine the association of reference vs biosimilar trastuzumab use with HF risk.

Among 5,135 patients identified, 43.9% received reference trastuzumab. Use of biosimilar trastuzumab increased from 0% in 2018 to 71.3% in 2024 (P < 0.001). The overall rate of HF was 5.9% (5.5% among reference trastuzumab users vs 6.3% among biosimilar trastuzumab users; P = 0.26). In multivariable analysis, there was no statistically significant difference in HF risk between patients treated with biosimilar trastuzumab and those treated with reference trastuzumab (adjusted HR [aHR]: 1.16; 95% CI: 0.92-1.46). Patients with a Charlson Comorbidity Index score ≥2 had a higher risk of HF than those with a score of 0 (aHR: 1.52; 95% CI: 1.11-2.08). Compared with patients aged 18 to 54 years, those aged 65 to 74 years (aHR: 1.61; 95% CI: 1.19-2.19) and ≥75 years (aHR: 1.95; 95% CI: 1.29-2.96) had a higher risk of HF.

As biosimilar trastuzumab use continues to increase, our findings provide reassurance regarding its cardiac safety in the management of early-stage human epidermal growth factor receptor 2 breast cancer. Additional studies with longer follow-up are needed to confirm these findings and evaluate long-term cardiac outcomes.