Neoadjuvant Trastuzumab Biosimilar vs Trastuzumab in HER2-Positive Early Breast Cancer
In a phase III trial reported in the Journal of Clinical Oncology, Pivot et al found equivalence of the trastuzumab biosimilar SB3 and the reference trastuzumab (Herceptin) in producing breast pathologic complete response in the neoadjuvant treatment of patients with HER2-positive early breast cancer.
Study Details
In the international double-blind trial, 875 patients from 97 sites were randomized between April 2014 and August 2015 to receive SB3 (n = 437) or European Union–sourced trastuzumab (n = 438) for 8 cycles concurrent with chemotherapy (4 cycles of docetaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide), followed by surgery and 10 additional cycles of adjuvant SB3 or trastuzumab. Overall, 800 patients, including 402 in the SB3 group and 398 in the trastuzumab group, completed neoadjuvant therapy and surgery, with these patients constituting the per-protocol population.
The primary endpoint was the rate of breast pathologic complete response, defined as no histologic evidence of residual invasive tumor cells in the breast, in the per-protocol population. Equivalence was achieved if the 95% confidence interval [CI] of the pathologic complete response ratio was within 0.785 to 1.546 or the 95% CI of the difference was within 13%.
Breast Pathologic Complete Response Rates
Breast pathologic complete response rates were 51.7% in the SB3 group and 42.0% in the trastuzumab group. The adjusted ratio of breast pathologic complete response was 1.259 (95% CI = 1.085–1.460), falling within the predefined equivalence margins.
The adjusted difference in breast pathologic complete response rates was 10.70% (95% CI = 4.13%–17.26%), with the lower limit falling within and the upper limit falling outside the equivalence margin. The rates of total pathologic complete response, defined as no residual invasive tumor cells in breast and axillary lymph nodes, were 45.8% and 35.8%, and overall response rates were 96.3% and 91.2%, respectively.
Adverse Events and Immunogenicity
The most common adverse events of any grade in both the SB3 and trastuzumab groups were neutropenia (67% vs 64%), alopecia (67% vs 63%), and nausea (31% vs 30%). Serious adverse events occurred in 10.5% vs 10.7% of patients. Among adverse events of special interest, infusion-related reaction occurred in 8.2% vs 10.0%, asymptomatic left-ventricular systolic dysfunction occurred in 0.9% vs 0.7%, and congestive heart failure occurred in 0.5% vs 0%. Antidrug antibodies were found in 0.7% vs 0%.
The investigators concluded: “Equivalence for efficacy was demonstrated between SB3 and [trastuzumab] on the basis of the ratio of [breast pathologic complete response] rates. Safety and immunogenicity were comparable.”
The study was supported by Samsung Bioepis.
Xavier Pivot, MD, PhD, of the University Hospital Jean Minjoz, Institut National de la Santé et de la Recherche Médicale 1098, Besançon, France, is the corresponding author of the Journal of Clinical Oncology article.
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