Objectives/purpose: To compare the safety of biosimilar trastuzumab with its reference product in a real-world setting using significant decreases in left ventricular ejection fraction (LVEF) as the primary endpoint.
Sample and setting: A retrospective chart review was conducted at a major public hospital oncology centre in Malaysia. The study included female HER2-positive early or locally advanced breast cancer patients initiating adjuvant treatment with one-year intravenous trastuzumab biosimilar (between 1 Jan 2014 and 24 Apr 2021) or reference product (between 30 Apr 2021 and 31 May 2023).
Procedure: Paper-based medical records of patients identified from chemotherapy compounding records were screened. Key exclusions were metastatic disease, treatment outside index periods, product switching, and incomplete LVEF data. Data were collected using a standardized form. Propensity score weighting (PSW) using the inverse probability of treatment weighting (IPTW) method adjusted for baseline covariates (age, race, body mass index [BMI], hypertension, diabetes mellitus, baseline LVEF, cumulative anthracycline dose, left-sided radiotherapy). Weighted logistic regression estimated Odds Ratios (ORs) and 95% Confidence Intervals (CIs) for the outcomes. A cost-minimization analysis was performed from a payer perspective.
Results: Of 440 patients identified, 142 were included (79 biosimilar, 63 reference product). PSW successfully balanced most baseline characteristics. Significant LVEF decrease (≥10% from baseline to <50%) occurred in 3.8% (n=3) biosimilar versus 1.6% (n=1) reference product patients (OR 4.25, 95%CI 0.41-44.1; p = 0.224). LVEF reduction of ≥16% from baseline occurred in 2.5% (n=2) of biosimilar versus 9.5% (n=6) reference product patients (OR 0.29, 95%CI 0.05-1.7; p=0.168). Cost ratio compared to pre-biosimilar registration were 47.5% (biosimilar registered, not in use) and 23.8% (biosimilar adoption).
Conclusion and clinical implications: No statistically significant differences were observed in cardiac safety in this real-world evidence approach using propensity score analysis. The findings warrant verification in larger, population-based studies. Biosimilar trastuzumab adoption achieved significant cost minimization.