In the last few years, five new biosimilar versions of trastuzumab (Herceptin) have been rigorously tested and approved by the FDA.

Article title: Biosimilars for breast cancer: a review of HER2-targeted antibodies in the United States

Citation: Miller EM & Schwartzberg LS. Ther Adv Med Oncol 2019;11:1–9

Publication date: November 2019

In the last few years, five new biosimilar versions of trastuzumab (Herceptin®) have been rigorously tested and approved by the FDA, although patent issues with the originator initially halted their market launch. With so many options becoming available, widespread adoption of trastuzumab biosimilars may depend on healthcare providers’ degree of comfort with evidence for their safety and efficacy.

Trastuzumab (Herceptin®) is approved in the USA for the treatment of early-stage and metastatic breast cancer overexpressing HER2. However, its high cost – at least $70,000 per year – can be a barrier to patient access. Due to their abbreviated approval processes, biosimilars including trastuzumab can potentially enter healthcare markets at lower cost than the original drug; hence biosimilar trastuzumab may provide patients an opportunity for expanded utilisation of this therapy.

Based on supporting evidence for their structural and functional similarity, equivalent pharmacological properties and efficacy versus originator product, the US FDA has approved five trastuzumab biosimilars for use in multiple indications to-date. The first of these biosimilars, named trastuzumab-tkst (Ogivri®), was evaluated clinically in a phase 3 trial in HER2+ metastatic breast cancer. This biosimilar, in combination with chemotherapy, was associated with a 69.9% overall response rate (ORR) compared with 64% for trastuzumab. Trastuzumab-tkst was FDA approved in 2017. Subsequently, four more trastuzumab biosimilars – namely trastuzumab-pkrb (Herzuma®; approved 2018), trastuzumab-dttb (Ontruzant®; 2019), trastuzumab-qyyp (Trazimera®; 2019), and trastuzumab-anns (Kanjinti®; 2019) – were assessed in phase III trials, all in the setting of HER2+ breast cancer, and demonstrated equivalent response rates and survival endpoints to those elicited by originator trastuzumab. Moreover, similar rates of adverse events were seen for biosimilar and trastuzumab groups in all studies.

Misconceptions on the level of evidence for biosimilars may pose a barrier to the utilisation of these drugs. Probably the most unfamiliar concept in the approval process for biosimilars is extrapolation of indications for which the originator biologic, but not the biosimilar, has been studied. However, scientific evidence to justify extrapolation based on biosimilarity is available for all approved products. Trastuzumab’s safety and efficacy are established for early-stage and metastatic breast cancer and metastatic gastric cancer. Based on the overall totality of evidence for trastuzumab biosimilars, they were also approved for the same indications. Uptake of these biosimilars will likely be proportionate with the level of confidence they inspire.

Key takeaway

Trastuzumab biosimilars have been approved based on the totality of evidence demonstrating biosimilarity to the reference product. Biosimilar uptake will be proportionate with the level of confidence inspired depending upon education of biosimilar efficacy and safety.