The arrival of biosimilar monoclonal antibodies in oncology: clinical studies for trastuzumab biosimilars

Abstract

The monoclonal antibody trastuzumab (Herceptin®), which targets the human epidermal growth factor receptor 2 (HER2), is approved for the treatment of early breast and advanced breast and gastric cancer in which HER2 is overexpressed. Several biosimilar versions of trastuzumab are expected to enter the European market over the course of 2018 and 2019. The biosimilar development pathway consists of a comprehensive comparability exercise between the biosimilar candidate and the reference product, primarily focussing on data from analytical studies. Clinical studies for biosimilar candidates follow a different design to those for a new biological, as the aim is not to independently establish clinical benefit, but to confirm biosimilarity between the two agents. The different trastuzumab biosimilar candidates have followed diverse pathways in their clinical development, with differences in clinical trial design (equivalence or non-inferiority design), patient population (those with metastatic or early breast cancer) and endpoint (overall response rate or pathological complete response). These differences in approach in phase 3 testing must be viewed in the totality of evidence demonstrating biosimilarity. Adequate information on the biosimilar approval pathway, the nature of the biosimilarity exercise and how the clinical development of a biosimilar is tailored to meet the licensing requirements can help informed decision making in clinical practice.

Economic evaluation of adjuvant trastuzumab therapy for HER2-positive early-stage breast cancer: systematic review and quality assessment

“…Nevertheless, it is noteworthy to highlight that six trastuzumab biosimilars have been recently approved by the European Union and are presently available in the market [54]. In effect, this has led to a significant price reduction by 20% to 30% [55].…”

Neoadjuvant chemotherapy and HER2 dual blockade including biosimilar trastuzumab (SB3) for HER2-positive early breast cancer: Population based real world data from the Danish Breast Cancer Group (DBCG)

“…The patent on trastuzumab (Herceptin) expired in the EU in 2014 leading to several new biosimilars being approved in 2017 and 2018 [ 20 ]. Biosimilars are not identical to their reference product due to intrinsic heterogeneity in these large complexes and can therefore not be equivalated to generic products [ 21 ].…”

Anti-ErbB2 immunotherapeutics: struggling to make better antibodies for cancer therapy

“…Therefore, biosimilar comparability exercises were performed in different patient populations (i.e., metastatic or early breast cancer patients), adopting different trial end points (i.e., overall response rate or pathological complete response). 32 Two analyses of the treatment costs of biosimilars compared to originator antibodies in Italy and Japan pointed to a potential economic advantage of trastuzumab biosimilars of about 30-40%. 33,34 In another study, the impact on economic burden for treating cancer from a payer's perspective upon the introduction of the Herceptin biosimilar CT-P6 (Herzuma) in 28 European countries was analyzed.…”