A trastuzumab biosimilar drug has shown an equivalent response, compared with trastuzumab, in the treatment of ERBB2 (HER2)-positive metastatic breast cancer, according to the results of a randomized double-blind controlled trial.
The anti-ERBB2 humanized monoclonal antibody trastuzumab in combination with chemotherapy has been found in numerous trials to significantly improve progression-free survival and overall survival in women with ERBB2-positive metastatic breast, compared with chemotherapy alone.
Dr. Hope S. Rugo
“With impending patent expiration of some biological agents, development of biosimilars has become a high priority for drug developers and health authorities throughout the world to provide access to high-quality alternatives,” the authors wrote. “A biosimilar drug is a biological product that is highly similar to a licensed biological product, with no clinically meaningful differences in terms of safety, purity, or potency.”
In a phase III multicenter trial, 500 women with ERBB2 (HER2)-positive metastatic breast cancer, recruited from 95 sites in Europe, Africa, South America, and Asia, were randomized 1:1 to intravenous infusions of trastuzumab or a biosimilar labeled MYL-1401O, with both arms also receiving taxane therapy.
At 24 weeks, the overall response rate (ORR) was not significantly different between the biosimilar and trastuzumab groups (69.6% vs. 64.0%; ORR ratio, 1.09; 90% confidence interval, 0.974-1.211) and within the predefined equivalence boundaries, the investigators report (JAMA. 2016 Dec 1. doi: 10.1001/jama.2016.18305).
By week 48, both groups also showed no significant differences in time to tumor progression, progression-free survival (44.3% vs. 44.7%), or overall survival (89.1% vs. 85.1%).
Pharmacokinetic analysis showed the mean concentrations of trastuzumab were similar for the two treatments, and minimum drug concentrations were also comparable at week 16 of treatment.
“This confirmatory efficacy and safety study was the last step in the multistep process to demonstrate similarity of a trastuzumab biosimilar and was adequately powered to demonstrate equivalence with trastuzumab,” the authors wrote. “The results of this study are consistent with the physicochemical and functional similarity shown in vitro and in vivo and with the similar pharmacokinetics shown in healthy participants between the candidate biosimilar and trastuzumab.”
This consistency also extended to adverse events. Almost all participants in both the biosimilar and the trastuzumab groups reported at least one adverse event, which included neutropenia (57.5% vs. 53.3%), peripheral neuropathy (23.1% vs. 24.8%), and diarrhea (20.6% vs. 20.7%).
“A biosimilar treatment option may increase global access to biological cancer therapies, provided, among other issues, that the price of the biosimilar is sufficiently inexpensive to enable women in non–high-income countries to access this therapy,” the authors wrote.
However, they pointed out that the stepwise development program for biosimilar drugs tended to use shorter end-points – 24 weeks for the primary endpoint and 48 weeks for secondary endpoints in this particular study. By 48 weeks, more than 50% of patients had not shown progression, suggesting that the medians for efficacy parameters may have been longer with a longer data cut-off.
“The choice of the 24-week evaluation period for part 1 of this study was related to the ability to analyze the ORR as a short-term measure of clinical activity and safety directly related to the combination of taxanes with trastuzumab and the proposed biosimilar as first-line treatment.”
The study was funded and sponsored by Mylan, which manufactured the biosimilar drug, and Biocon Research Limited. Four authors declared stock in Mylan, two declared consulting fees from Mylan and one also declared stock in Biocon Research Limited. One author declared research and travel support from other pharmaceutical companies.