CHICAGO — MYL-1401O, a biosimilar trastuzumab antibody, appeared to have comparable safety and efficacy to its FDA–approved reference product in women with HER-2–positive advanced breast cancer, according to results of a randomized phase 3 study presented at the ASCO Annual Meeting.
The addition of trastuzumab (Herceptin, Genentech) — a biologic agent approved by the FDA in 1998 and now indicated for women with early- or late-stage breast cancer — to chemotherapy has resulted in a 5- to 8-month survival improvement for women with late-stage disease. The addition of 1 year of trastuzumab to chemotherapy also reduces the risk for recurrence by 10% and improves survival by about 9% in women with early-stage disease.
Hope S. Rugo
“Biologic agents are usually targeted therapies and are costly, limiting access across the globe,” Hope S. Rugo, MD, professor of medicine at University of California, San Francisco, said during a press conference. “Many biologic agents are losing patent protection soon, or have already lost patent protection in other countries. Biosimilars have the potential to significantly improve access to expensive agents.”
Regulatory agencies have established requirements for biosimilar approval. They include a demonstration of structural and functional similarity to the reference product; a demonstration of similar pharmacokinetics and pharmacodynamics; and confirmation of similar safety, efficacy and immunogenicity.
Rugo and colleagues evaluated the safety, efficacy and immunogenicity of MYL-1401O (Mylan Inc.) compared with trastuzumab.
The analysis included data from 458 women treated at 95 sites worldwide. All women had HER-2–positive metastatic breast cancer, and they had not received prior chemotherapy or trastuzumab for metastatic disease. Forty-four percent of women had hormone receptor–positive disease.
Researchers randomly assigned patients to receive Myl-1401O (n = 230) or trastuzumab (n = 228) with docetaxel or paclitaxel every 3 weeks for at least eight cycles. Patients with stable disease beyond the eighth cycle could continue to receive the antibody therapy alone until disease progression or unacceptable toxicity.
Overall response rate at week 24 served as the study’s primary endpoint. The FDA also asked researchers to calculate ORR ratio as an endpoint, and the European Medicines Agency asked for the difference in ORR between the proposed biosimilar and trastuzumab. Secondary endpoints included PFS, OS and safety.
At week 24, the ORR rate was 69.6% for Myl-1401O and 64% for trastuzumab. Researchers calculated an ORR ratio of 1.09 (90% CI, 0.97-1.21; and 95% CI, 0.95-1.23), meeting the predefined equivalency margin. The difference in ORR was 5.5 (90% CI, –1.7 to 12.69; and 95% CI, –3.08 to 14.04), which also fell within the required equivalency range.
Based on 41 events in the biosimilar arm and 48 in the reference product arm, median PFS had not yet been reached.
The overall antidrug antibody rate was 2.4% with Myl-1401O and 2.8% with trastuzumab, consistent with published data, Rugo said. The dose-normalized maximum concentration and area under the curve also were similar between the two agents.
Safety appeared comparable between study groups, and no significant changes in cardiac function occurred in either cohort. Serious adverse events — which were primarily hematologic and related to taxane therapy — occurred in 38.1% of those assigned the biosimilar and 36.2% of those assigned the reference product. Common adverse events included neutropenia (biosimilar, 27.5%; reference product, 25.2%) febrile neutropenia (4.5% vs. 4.1%), leukopenia (1.6% vs. 4.9%) and pneumonia (1.6% vs. 2%).
Four fatal events occurred in each study arm.
“This proposed biosimilar has the potential to meet the need for an affordable treatment option for patients with HER-2–positive cancers,” Rugo said. “This is one of the first trials of biosimilars in oncology to demonstrate these similar results. Ongoing trials with other biosimilars should further improve access worldwide to these lifesaving therapies.” – by Alexandra Todak
Reference: Rugo HS, et al. Abstract LBA503. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Disclosure: The study was funded in part by Mylan. Rugo reports a speakers bureau role with and honoraria from Genomic Health; travel expenses from Mylan, Nektar, Novartis, OBI Pharma and Roche/Genentech; and institutional research funding from Celsion, Eisai, Genentech, MacroGenics, Merck, Nektar, Novartis, OBI Pharma, Pfizer and Plexxikon. Please see the abstract for a list of all other researchers’ relevant financial disclosures.