This comparative clinical trial evaluated efficacy, safety, immunogenicity and pharmacokinetics (PK) of PF-05280014, a potential trastuzumab biosimilar, vs trastuzumab sourced from the EU (trastuzumab-EU), both given with D and C, as neoadjuvant treatment for operable HER2+ breast cancer.
Patients (pts; N = 226) were stratified by primary tumor size and hormone receptor status and randomized 1:1 to receive PF-05280014 or trastuzumab-EU (8 mg/kg at Cycle 1; 6 mg/kg thereafter), both with D (75 mg/m2) and C (target AUC 6), every 3 wks for 6 treatment cycles. The study was powered to test whether PF-05280014 was noninferior to trastuzumab-EU in the percentage of pts with Cycle 5 Ctrough (pre-dose Cycle 6) >20 μg/mL. Efficacy was measured by the percentage of pts with pathological complete response (pCR), defined as the absence of invasive neoplastic cells in breast and lymph nodes after neoadjuvant therapy, and objective response rate (ORR). Safety and immunogenicity were also assessed.
The percentage of pts with Cycle 5 Ctrough >20 μg/mL was 92.1% for PF-05280014 and 93.3% for trastuzumab-EU; the lower limit of the 95% CI (-8.02% to 6.49%) for the stratified difference between groups was above the noninferiority margin (-12.5%). The pCR rate was 47.0% (95% CI: 36.9-57.2) for PF-05280014 and 50.0% (95% CI: 39.0-61.0) for trastuzumab-EU. Central radiology review-assessed ORR was 88.1% (95% CI: 80.2-93.7) for PF-05280014 and 82.0% (95% CI: 72.5-89.4) for trastuzumab-EU. All causality, grade 3-4 treatment-emergent adverse events were reported by 38.1% (PF-05280014) vs 45.5% (trastuzumab-EU) of pts. No pts in the PF-05280014 and 1 (0.89%) in the trastuzumab-EU group had positive anti-drug antibody titer.
PF-05280014 demonstrated similarity in efficacy, safety and immunogenicity, and noninferiority in PK to trastuzumab-EU. A separate comparative safety and efficacy study (NCT01989676) is evaluating PF-05280014 vs trastuzumab-EU, both given with paclitaxel, as first-line treatment for HER2+ metastatic breast cancer.
Clinical trial identification
NCT02187744; EudraCT No: 2013-004679-11
Legal entity responsible for the study
P.E. Lammers: Advisory boards with Pfizer Inc. M. Dank: Member of Biosimilars Oncology European Advisory Board with Pfizer Inc since 2013. R. Abbas, F. Hilton, J. Coiro, I. Jacobs: Full time employee and lares stock holdings and/or stock options from Pfizer Inc. All other authors have declared no conflicts of interest.