Although biosimilar supportive care agents have generally been accepted by oncologists, the same cannot be said for biosimilars that are intended to treat cancers themselves. A survey among community oncologists in the United States showed that some respondents reported being “uncomfortable or unfamiliar” with the current regulatory process for biosimilars.
To help close this knowledge gap, the evidence used to support the regulatory approval of a biosimilar in oncology was explained by experts recently in the Journal of Clinical Oncology. In particular, the article authors explained the role of comparative clinical studies in biosimilar development and how they differ from the traditional phase 3 studies used to evaluate novel agents.
The purpose of comparative clinical studies is “not to demonstrate clinical benefit.” Instead, the purpose is to “confirm clinical equivalence of the potential biosimilar and reference product.” As a result, comparative clinical studies may use short-term surrogate endpoints, like overall response rate or pathologic complete response, instead of an endpoint that demonstrates clinical benefit, like overall survival or progression-free survival.
Once clinical equivalency to the reference product is shown, biosimilars can expand their label to include additional therapeutic indications without the need for more clinical studies, also known as extrapolation. In fact, this was done for 5 trastuzumab biosimilars initially approved for breast cancer.
In addition, unlike noninferiority studies, which are statistically designed to be one-sided, comparative clinical studies are two-sided, meaning the treatment effect for a biosimilar cannot be better or worse than the reference product in order to be considered equivalent.
However, if the treatment effect for the biosimilar does appear better, as was the case for 2 trastuzumab biosimilars — SB3 and ABP 980 — that does not negate the possibility of a regulatory approval. Again, unlike the development of reference products, biosimilar products are evaluated on the “totality of the evidence” and the foundation of this evidence is not clinical data but “comprehensive and robust” analytical data.
Stebbing J, Mainwaring PN, Curigliano G, et al. Understanding the role of comparative clinical studies in the development of oncology biosimilars [published online February 14, 2020]. J Clin Oncol. doi: 10.1200/JCO.19.02953