Efficacy of Trastuzumab Biosimilars Shown Equivalent to Originator in HER2 Breast Cancer
Two trastuzumab biosimilars show therapeutic equivalence to originator trastuzumab treating HER2-positive breast cancer, studies show.
|The following article features coverage from the 2017 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois. Click here to read more of Oncology Nurse Advisor's conference coverage.|
CHICAGO — Two trastuzumab biosimilars show therapeutic equivalence to originator trastuzumab as adjuvant treatment for HER2-positive early breast cancer, according to the findings of separate studies presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.
A team led by Xavier B. Pivot, MD, of the University Hospital of Besançon, France, compared SB3 and originator trastuzumab in a phase 3 double-blind randomized trial that included 875 patients with HER2-positive early breast cancer or locally advanced breast cancer. They randomly assigned 437 patients to the trastuzumab biosimilar (SB3) arm and 438 to the originator trastuzumab arm. The investigators defined equivalence as a 90% confidence interval (CI) of the ratio of breast pathologic complete response (bpCR, SB3/originator trastuzumab) of 0.785 to 1.546 or 95% CI of the difference in bpCR rates of –13% to 13%.1
In a per-protocol set (PPS) — patients who completed neoadjuvant therapy and surgery without prespecified major protocol deviations — the bpCR rate was 51.7% in the SB3 arm and 42.0% in the originator trastuzumab arm. In the full analysis set, the rate was 51.1% in the SB3 arm and 41.9% in the originator trastuzumab arm. The adjusted ratio was 1.249 (90% CI, 1.112-1.426), which was within the predefined margin, Dr Pivot's team reported. The adjusted difference was 10.70% (95% CI, 4.13%-17.26%), with the lower margin contained within and the upper margin outside the predefined margin.
SB3 was well tolerated, with safety, pharmacokinetics, and immunogenicity comparable to originator trastuzumab, according to the investigators.1
For the other study, which was double-blind, Justin Stebbing, MD, PhD, of Imperial College Healthcare NHS Trust in London, United Kingdom, and colleagues randomly assigned 549 patients with HER2 early breast cancer to receive the CT-P6 biosimilar (271 patients) or originator trastuzumab (278 patients). The primary objective was to demonstrate therapeutic equivalence as determined by pathologic complete response (pCR). The predefined therapeutic equivalence margin was a 95% CI of 0.74 to 1.35 for the risk ratio and a risk difference of ±15%.2
The equivalence was demonstrated in both a PPS and intent-to-treat set (ITT). The risk ratio estimate for pCR was 0.93 for the PPS (CI, 0.78-1.11) and 0.92 for ITT set (CI, 0.77-1.11). The estimated risk difference was –3.62 (CI, –12.38-5.16) for the PPS and –3.58 (CI, –11.98-4.80) for the ITT set.
In the PPS, the pCR rates for CT-P6 and originator trastuzumab were 46.8% and 50.4%, respectively. In the ITT set, the rates were 43.5% and 47.1%, respectively. With respect to breast pCR, the pCR rates for CT-P6 and reference trastuzumab were 51.6% and 55.1% in the PPS, respectively, and 49.1% and 52.2% in the ITT set, respectively.
The 2 treatment arms had similar proportions of patients with grade 3 or higher treatment-emergent adverse events (8.6% in the CT-p6 arm and 10.1% in the originator trastuzumab arm). Pharmacokinetic and pharmacodynamic results were similar between the groups.2
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1. Pivot X, Bondarenko I, Dvorkin M, et al. A randomized, double-blind, phase III study comparing SB3 (trastuzumab biosimilar) with originator trastuzumab in patients treated by neoadjuvant therapy for HER2-positive early breast cancer. Poster presentation at: 2017 American Society of Clinical Oncology Annual Meeting; June 2-6, 2017; Chicago, IL.
2. Stebbing J, Baranau YV, Baryash V, et al. Double-blind, randomized phase 3 study to compare the efficacy of CT-P6, trastuzumab biosimilar candidate, versus reference trastuzumab as neoadjuvant treatment in HER2 positive early breast cancer (EBC). Poster presentation at: 2017 American Society of Clinical Oncology Annual Meeting; June 2-6, 2017; Chicago, IL.