Results from the phase 3 REFLECTIONS B327-02 study in patients with HER2-positive metastatic breast cancer (MBC) were first presented in abstract form, but have now been reported in detail.
In July 2018, the European Commission authorized the Pfizer’s PF-05280014, a trastuzumab biosimilar referencing Herceptin, under the brand name Trazimera. The marketing approval followed a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use, which relied on Pfizer’s data package that included results from the phase 3 REFLECTIONS B327-02 study. The study’s results were first presented in abstract form at the European Society for Medical Oncology conference in 2017 but have now been reported in detail the British Journal of Cancer.
In the ongoing, international, randomized, double-blind, parallel-group study, 707 female patients with HER2-positive metastatic breast cancer (MBC) were randomized at 143 sites in 24 countries. Exclusion criteria include prior systemic therapy, except for endocrine therapy.
Patients received either the biosimilar (n = 352) or the EU-licensed reference trastuzumab (n = 355) together with paclitaxel. Upon completion of the paclitaxel administration period, no earlier than week 33, the trastuzumab regimen could be changed at the investigators’ discretion, though dose reductions were not allowed, and treatment could continue until disease progression.
The study’s primary endpoint was objective response rate (ORR), which regulators considered sufficiently sensitive to detect any clinically meaningful differences in efficacy between the biosimilar and the reference. ORR was measured as the percentage of patients in each group with complete or partial response at week 25 that was confirmed at week 33. The investigators prespecified that equivalence would be determined if the 95% CI of the risk ratio for ORR fell within the margin of 0.80 to 1.25.
The risk ratio for ORR by week 25, confirmed by week 33, in the intention-to-treat (ITT) population was 0.940, with a 95% CI of 0.842-1.049, which fell within the prespecified equivalence margin. ORR in the biosimilar group was 62.5% (95% CI, 57.2%-67.6%) versus 66.5% (95% CI, 61.3%-71.4%) in the reference group. The risk difference for ORR was −4.0% (95% CI, −11.0% to 3.1%).
At week 53, disease progression or death in the ITT population was reported for 40.9% of the patients in the biosimilar group and 41.7% of patients in the reference group. The respective estimated 1-year progression-free survival (PFS) rates were 54% (95% CI, 48%-60%) and 51% (95% CI, 45%-57%). Median respective times to PFS were 12.16 (95% CI, 11.93-12.48) months and 12.06 (95% CI, 11.79-not estimable) months.
Estimated 1-year overall survival rates were 89.31% (95% CI, 85.48%-92.17%) in the biosimilar group versus 87.36% (95% CI, 83.27%-90.51%) in the reference group.
At week 53, most patients (96.6% in the biosimilar arm and 96.0% in the reference arm) in the safety population had experienced at least 1 treatment-emergent adverse event (AE). The incidence for all AEs was similar between groups, with alopecia, anemia, neutropenia, and peripheral sensory neuropathy being the most commonly reported. Serious AEs were reported in 20.1% of patients in the biosimilar arm and 20.7% of patients in the reference arm, with disease progression, pulmonary embolism, and pneumonia being the most common serious AEs.
In total, 2 patients, 1 from each group, tested positive for antidrug antibodies (ADAs) and neutralizing antibodies (NABs) at the end-of-treatment visit. One of the 2 patients was also positive for both ADAs and NABs at baseline.
The investigators concluded that, when used as a first-line treatment for HER2-positive MBC, the biosimilar, used together with paclitaxel, demonstrated equivalence to the EU-licensed Herceptin plus paclitaxel in terms of ORR. The investigators noted that the study is ongoing, and the database lock will take place when long-term follow-up is complete.
While Pfizer’s biosimilar has demonstrated equivalence to the EU reference, the product is not yet authorized in the United States; in April 2018, Pfizer received a Complete Response Letter from the FDA for the drug. Pfizer indicated at the time that the FDA had highlighted the need for additional technical information, but it clarified that the FDA did not request any additional safety or clinical data. The company stated that it would work closely with the FDA to address the agency’s questions and remained committed to developing the biosimilar.
Reference
Pegram MD, Bondarenko I, Zorzetto MMC, et al. PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomized, double-blind study. Brit J Cancer. 2019;120:172-182. doi: 10.1038/s41416-018-0340-2.
Biosimilars Oncology Roundup for June 2024—Podcast Edition
July 7th 2024On this episode of Not So Different, we review biosimilar news coming out of June, with clinical trial results from conferences and a study showcasing how to overcome economic and noneconomic barriers to oncology biosimilars.
Similar Survival, Safety for Bevacizumab Biosimilar vs Originator in Colorectal Cancer
February 8th 2025A retrospective observational study found no significant differences in progression-free survival or safety in patients with colorectal cancers in Japan treated with ABP 215, Amgen’s bevacizumab biosimilar, or reference bevacizumab (Avastin), and estimated cost savings of 800,000 Japanese yen (approximately $5100) per patient with the biosimilar.
A New Chapter: How 2023 Will Shape the US Biosimilar Space for 2024 and Beyond
December 31st 2023On this episode of Not So Different, Cencora's Brian Biehn and Corey Ford take a look back at major policy and regulatory advancements in 2023 and how these changes will alter the space going forward.
The Biosimilar Void: 90% of Biologics Coming Off Patent Will Lack Biosimilars
February 5th 2025Of the 118 biologics losing exclusivity over the next decade, only 10% have biosimilars in development, meaning a vast majority of biologics have no pipeline, which limits savings potential for the health care system.
A Banner Year for Biosimilars: The 19 FDA Approvals From 2024
January 21st 2025In 2024, the FDA approved 19 biosimilars across various therapeutic areas, including the first biosimilars for ustekinumab and denosumab, marking significant progress in expanding treatment options and market competition.