Equivalence Trial of Neoadjuvant Trastuzumab Biosimilar CT-P6 vs Trastuzumab in HER2-Positive Breast Cancer

Key Points

  • The proposed trastuzumab biosimilar CT-P6 had equivalent efficacy vs reference trastuzumab in the neoadjuvant treatment of HER2-positive early breast cancer.
  • Safety profiles were similar.

A phase III equivalence trial has shown comparable pathologic complete response rates with the proposed trastuzumab biosimilar CT-P6 vs reference trastuzumab (Herceptin) in neoadjuvant treatment of HER2-positive early breast cancer. The study was reported by Stebbing et al in The Lancet Oncology.

Study Details

In the double-blind trial, 549 women with stage I to IIIa disease from 112 sites in 23 countries were randomized between August 2014 and May 2016 to receive neoadjuvant intravenous CT-P6 (n = 271) or trastuzumab (n = 278) for eight 3-week cycles (8 mg/kg on day 1 of cycle 1 and 6 mg/kg on day 1 of cycles 2–8) along with docetaxel (75 mg/m² on day 1 of cycles 1-4) and FEC (fluorouracil at 500 mg/m², epirubicin at 75 mg/m², and cyclophosphamide at 500 mg/m² on day 1 of cycles 5–8). The primary efficacy endpoint was pathologic complete response in the per-protocol population according to masked central review of local histopathology reports.

Pathologic Complete Response

Among 248 CT-P6 patients and 256 trastuzumab patients in the per-protocol population, pathologic complete response was achieved in 46.8% (95% confidence interval [CI] = 40.4%–53.2%) of the CT-P6 group and in 50.4% (95% CI = 44.1%–56.7%) of the trastuzumab group. The 95% confidence interval of the estimated treatment outcome difference (–0.04%, 95% CI = –0.12 to 0.05) was within the prespecified equivalence margin (–0.15 to 0.15). In the intention-to-treat population, response rates were 43.5% (95% CI = 37.6%–49.7%) vs 47.1% (95% CI = 41.1%–53.2%; difference = –0.04, 95% CI = –0.12 to 0.05).

Adverse Events

Grade ≥ 3 treatment-related adverse events occurred in 6% of the CT-P6 group vs 8% of the reference trastuzumab group, with the most common in both groups being neutropenia (4% vs 5%). Serious adverse events occurred in 7% vs 8%, including febrile neutropenia (1% vs < 1%) and neutropenia (< 1% vs 1%). Among treatment-related adverse events of special interest, cardiac disorders occurred in 6% vs 6%, infection occurred in 4% vs 4%, and infusion-related reactions occurred in 5% vs 5%.

The investigators concluded: “CT-P6 showed equivalent efficacy to reference trastuzumab and adverse events were similar. Availability of trastuzumab biosimilars could increase access to this targeted therapy for HER2-positive early-stage cancer.”

The study was funded by Celltrion Inc.

Francisco J. Esteva, MD, of New York University Langone Medical Center, is the corresponding author of The Lancet Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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