A biosimilar is a biologic product that is highly similar to an approved biologic drug. The humanized monoclonal antibody PF-05280014 (a potential trastuzumab biosimilar) has previously demonstrated similarity to trastuzumab in analytical, nonclinical, and clinical pharmacokinetics (PK) and safety studies. In this randomized, double-blind, efficacy and safety study, PF-05280014 was compared with trastuzumab sourced from the EU (trastuzumab-EU) as first-line treatment for patients (pts) with HER2-positive (HER2+) metastatic breast cancer (MBC).
Between 4 Apr 2014 and 22 Jan 2016, 707 pts with HER2+ MBC were randomized 1:1 to PF-05280014 or trastuzumab-EU, both given with paclitaxel (starting dose 80 mg/m2; days 1, 8, 15 of each 28-day cycle). Trastuzumab was administered weekly until at least Week 33 (first dose 4 mg/kg; subsequent doses 2 mg/kg), with treatment continuing until progression. The primary endpoint was objective response rate (ORR; complete or partial response according to RECIST 1.1) by Week 25 and confirmed by Week 33, based on blinded central radiology review. Secondary endpoints included safety, measures of tumor control, immunogenicity, and PK.
The risk ratio for ORR was 0.940 for PF-05280014 over trastuzumab-EU, with a 95% confidence interval of 0.842–1.049, which was within the pre-specified equivalence margin of 0.8–1.25. 1-yr progression-free survival (56% for PF-05280014 vs 52% for trastuzumab-EU) and 1-yr survival (88.84% vs 87.96%) were similar between groups. The safety profile, including incidence of serious adverse events, was similar in both arms, and no new safety signals were identified. After study drug initiation, all pts tested negative for antidrug antibodies, except 1 pt receiving trastuzumab-EU. Up to cycle 5 day 8, mean trough and peak serum concentrations were similar for both agents. At the cutoff for this primary analysis (24 Aug 2016), 558 pts remained ongoing in the study.
In pts receiving first-line treatment for HER2+ MBC, PF-05280014 was similar to trastuzumab-EU in terms of efficacy, safety, immunogenicity, and PK.
Clinical trial identification
NCT01989676; EudraCT number: 2013-001352-34
Legal entity responsible for the study
This study was sponsored by Pfizer Inc
M. Pegram: Consulting: Pfizer Inc, Amgen Inc, Genentech/Roche. A. Freyman, A. Vana, F. Hilton, C. Zacharchuk, R. Ewesuedo: Employee of and holds stock or stock options in Pfizer Inc. All other authors have declared no conflicts of interest.