Evaluating External Validity of Oncology Biosimilar Safety Studies

Biologics are the fastest growing medication class in the US and account for an increasing portion of health care costs. In the US, the Biologics Price Competition and Innovation Act of 2009 created an abbreviated approval pathway to expand access to safe and effective biological products.¹ Pivot et al² report the results of a phase 3 randomized trial of SB3, a trastuzumab biosimilar approved by the US Food and Drug Administration (FDA) in 2019, in the largest and longest follow-up study to date comparing cardiac safety and survival with its originator product, reference trastuzumab. Trastuzumab is a monoclonal antibody human epidermal growth factor receptor 2 (ERBB2) antagonist indicated for treatment of ERBB2-overexpressing breast cancer. Use of ERBB2-targeted therapy is the standard of care for patients with ERBB2-overexpressing tumors in most clinical scenarios. Despite clear clinical guidelines, previous studies indicate that up to 28% of patients with ERBB2-overexpressing early-stage breast cancer do not receive ERBB2-targeted therapy³ and that cost of treatment is the greatest reported barrier, especially in low-income and middle-income countries.⁴ In the US, there are also racial inequities, whereby Black patients, who are disproportionately burdened with financial toxicity and other structural barriers to cancer care, are less likely than their White counterparts to receive trastuzumab.⁵ The entry of oncology biosimilars such as SB3 into a stable, competitive market represents a potential for cost savings and increased access to these treatments, especially among patients for whom cost is a barrier to receipt of optimal therapy. Here, we apply a health equity lens to the evaluation of biosimilar safety and consider long-term follow-up studies of oncology biosimilars and their corresponding external validity in relation to health equity. As with other medical advances, biosimilars have the potential to reduce or exacerbate health inequities depending on whether studies supporting regulatory approval exclude marginalized populations as commonly occurs, thus impacting external validity, and whether uptake remains disparate across racial and ethnic populations.