Study Shows CT-P6 Has Equivalent Efficacy to Reference Trastuzumab for HER2-Positive Breast Cancer

CT-P6, a proposed biosimilar of trastuzumab, showed equivalent efficacy to reference trastuzumab (Genentech’s Herceptin) as a neoadjuvant treatment in human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer, according to a recent phase 3 equivalence trial. CT-P6 is produced by Celltrion, and is an approved biosimilar in the Republic of Korea. The study, conducted by Justin Stebbing, MD, of Imperial College Healthcare NHS Trust, London, United Kingdom, and colleagues, was published in the July issue of The Lancet Oncology.

The researchers recruited women, 18 years of age and older, who had stage I to IIIA operable HER2-positive breast cancer from 112 centers in 23 countries. The study’s inclusion criteria included a performance status score of 0 or 1 on the Eastern Cooperative Oncology Group criteria; adequate bone marrow, hepatic, and renal function; at least 1 measureable lesion; and known estrogen and progesterone receptor status. The study excluded women with bilateral breast cancer, previous breast cancer treatment, previous anthracycline treatment, and pregnancy or lactation.

Between August of 2014 and May of 2016, 549 patients were randomly assigned in a 1:1 ratio to receive neoadjuvant CT-P6 (n = 271) or reference trastuzumab (n = 278) intravenously for 8 cycles along with neoadjuvant docetaxel and fluorouracil (FEC), epirubicin, and cyclophosphamide therapy. Surgery was performed within 3 to 6 weeks of the final neoadjuvant study drug dose, followed by an adjuvant treatment period of up to 1 year. All participants and investigators were masked as to treatment until the study was completed.

The researchers monitored the long-term safety and efficacy of the trastuzumab biosimilar for 3 years after the last patient was enrolled in the study. The study’s primary efficacy endpoint was pathological complete response (defined as the absence of invasive cancer in the breast and axillary nodes, assessed by histopathology reports obtained after surgery). The equivalence margin (EM), a measure of clinically meaningful differences in effectiveness between the biosimilar and reference product, was set at -0.15 to 0.15.

The study reports that a similar proportion of patients achieved pathological complete response with CT-P6 (116 of 248 patients, or 48.8%) as with reference trastuzumab (129 of 256 patients, or 44.1%). The researchers stated that the estimated treatment outcome difference was within the set EM.

Serious treatment-emergent adverse events (AEs) were reported by 7% of the patients in the CT-P6 group versus 8% of the reference trastuzumab group; frequent, serious AEs were febrile neutropenia (1% vs <1%) and neutropenia (<1% vs 1%). Grade 3 or worse treatment-related AEs occurred in 6% of 271 patients in the CT-P6 group versus 8% of 278 in the reference trastuzumab group. The most frequently reported AE was neutropenia in 4% versus 5%.

The investigators concluded that the study’s findings of CT-P6’s equivalent efficacy to reference trastuzumab and its similar adverse event profile suggest that availability of trastuzumab biosimilars could increase access to this targeted therapy for HER2-positive early-stage cancer.