Biosimilars: New Avenues for the Practicing Oncologist Treating Breast Cancer

Oncologists attending the European Society for Medical Oncology (ESMO) 2018 Congress, held October 19–23 in Munich, have learned that biosimilars to trastuzumab demonstrated equal efficacy to the reference product in both early and metastatic breast cancer (MBC) settings. The research was presented this week.

These findings are reassuring to practicing oncologists, an expert in breast cancer told Cancer Network. “There are rigorous steps that must be met to arrive at the label of biosimilar compared to the originator,” said William J. Gradishar, MD, FASCO, FACP, who is a Betsy Bramsen professor of breast oncology and a professor of medicine, as well as chief in the Division of Hematology/Oncology, deputy director of the Clinical Network, and director of the Maggie Daley Center for Women’s Cancer Care, all at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at the Northwestern University Feinberg School of Medicine in Chicago.

The researchers conducted a systematic review to evaluate whether demonstrating bioequivalence in terms of efficacy differs between early breast cancer (EBC) and MBC. MEDLINE and conference abstracts that included the terms “biosimilar” and “trastuzumab” were identified from between January 1, 2013 and March 14, 2018. The investigators manually reviewed the abstracts and manuscripts to assess whether efficacy data for trastuzumab-dkst vs reference trastuzumab were available.

Of 84 results obtained, they selected 8 phase III clinical trials for 6 proposed biosimilars: 4 in EBC and 4 in MBC. The proposed biosimilar had equivalent efficacy to reference trastuzumab in all trials.

All of the biosimilars included in the analysis demonstrated equivalent efficacy to reference trastuzumab, regardless of the clinical setting. Two biosimilars-CT-P6 and PF-05280014-were equally effective in both the EBC and MBC settings.

In December 2017, the US Food and Drug Administration approved trastuzumab-dkst (Ogivri™), a biosimilar to trastuzumab, for the treatment of patients with breast cancer or metastatic stomach cancer whose tumors are human epidermal growth factor 2 (HER2)–positive. This approval was made based on phase III efficacy and safety data in metastatic breast cancer (MBC) as well as the agent’s physicochemical and functional biosimilarity. In the United States, trastuzumab-dkst is the first biosimilar to be approved for breast cancer or stomach cancer, and the second biosimilar to be approved for cancer.

“Although the FDA and European Medicines Agency determine biosimilarity based on totality of evidence, both the EBC and MBC settings appear to have similar sensitivity and be appropriate for determination of equivalent efficacy based on regulatory guidelines and clinical results. Together, these data support extrapolation between settings,” the researchers wrote in the abstract.

“It is the ‘totality of evidence’ that has been generated which should allow clinicians to feel comfortable that biosimilar trastuzumab(s) can be used in EBC and MBC,” Gradishar said.