Study Finds Trastuzumab Biosimilar Demonstrates Equivalence in Response Rates

A randomized, double-blind study published in the British Journal of Cancer compared the treatment regimen of paclitaxel plus trastuzumab biosimilar PF-05280014 or trastuzumab sourced from the European Union (trastuzumab-EU) as first-line therapy for human epidermal growth factor receptor 2-positive metastatic breast cancer. They found that both regimens resulted in similar objective response rates (ORRs; primary endpoint).

This ongoing, international, randomized, double-blind, parallel-group study included 707 patients from 143 sites in 24 countries. Eligible patients were adult females with metastatic, histologically confirmed breast cancer with at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumours.

Between April 4, 2014, and January 22, 2016, patients were randomized 1:1 to receive intravenous PF-05280014 plus paclitaxel (n=352) or trastuzumab-EU (n=355). PF-05280014 and trastuzumab-EU were administered weekly at a first dose of 4 mg/kg and subsequent dose of 2 mg/kg. Patients could change to a three-weekly regimen (6 mg/kg) at week 33. Patients continued treatment until disease progression. Paclitaxel was administered at a starting dose of 80 mg/m² on days one, eight, and 15 of 28-day cycles for at least six cycles or until maximal benefit.

At data cutoff (January 11, 2017), 536 randomized patients (75.8%) remained on study: 336 (47.5%) were still actively treated with PF-05280014 or trastuzumab-EU, while 200 (28.3%) had discontinued treatment but were being followed for survival. Disease progression was the primary reason for discontinuation of PF-05280014 (n=138; 39.2%) or trastuzumab-EU (n=143; 40.3).

The risk ratio for ORR was 0.940 (95% CI, 0.842-1.049, falling within the prespecified equivalence margin of 0.80 to 1.25). The ORR was 62.5% (95% CI, 57.2-67.6) in the PF-05280014 group and 66.5% (95% CI, 61.3-71.4) in the trastuzumab-EU group, for a risk difference of −4.0% (95% CI, −11.0-3.1).

At data cutoff, survival was similar between cohorts: Median progression-free survival (PFS) was 12.16 months in the PF-05280014 group and 12.06 months in the trastuzumab-EU group. The one-year PFS rate was 54% and 51%, respectively. The median overall survival (OS) was not reached in either group, and the one-year OS was 89.31% and 87.36%, respectively.

Most patients in the safety cohort experienced one or more treatment-related adverse events (AEs), including 337 patients (96.6%) in the PF-05280014 group and 339 (96.0%) in the trastuzumab-EU. The most common AEs in both groups were alopecia, anemia, neutropenia, and peripheral sensory neuropathy. The researchers noted no differences in the incidences of AEs of special interest between either cohort.