Biosimilar Trastuzumab in Clinical Trials: Differences or Not?

In the last decade, cancer therapies have increasingly taken the form of combination treatments in which biologic agents play a crucial role. In breast cancer, the treatment strategy is adjusted to intrinsic subtypes such as human epidermal growth factor receptor-2(HER2)-positive. With the introduction of trastuzumab, a monoclonal antibody against HER2, survival has significantly improved in early and metastatic breast cancer. Trastuzumab's patent has now expired and biosimilars are moving into the market. Several clinical trials have led to the approval of 5 different biosimilar trastuzumabs. Results proved similarity between the proposed biosimilar and the reference product without significant differences in efficacy and safety, although follow-up has been short. However, the shorter drug development process with its goal of showing similarity rather than patient benefit uses surrogate endpoints such as pathologic complete response and overall response rate, not survival endpoints in terms of the 'gold standarD' in evaluating cancer therapies. The aim of this article is to give insight into how to plan and perform a clinical trial to prove equivalence between a biosimilar trastuzumab and its reference product and to elucidate the setup and outcome of published clinical trials.