ADVERTISEMENT
Biosimilar vs Referent Trastuzumab for the Neoadjuvant Treatment of ERBB2–Positive Breast Cancer
HD201, a biosimilar to trastuzumab, demonstrated equivalence to referent trastuzumab in achieving a total pathological complete response and in safety in ERBB2–positive, early breast cancer, according to results from the phase 3 TROIKA trial (JAMA Oncol. 2022; doi:10.1001/jamaoncol.2021.8171). Formerly known as HER2, ERBB2 is a gene that encodes for the receptor tyrosine-protein kinase erbB-2.
“The TROIKA study represents an important step on the path of registration for routine use for HD201,” wrote Xavier Pivot, MD, PhD, Institute of Cancer, Strasbourg, France, and colleagues. “The introduction of trastuzumab into the therapeutic armamentarium for ERBB2–positive breast cancer has substantially changed the natural history of this disease," they wrote, adding "However, the high cost of referent trastuzumab therapy is a burden for health care systems, and, in many countries, patients have only limited access because of the high costs." Introducing new biosimilars may address the need for less expensive alternatives to referent trastuzumab.
In the trial, which was done in 70 centers in 12 countries in Western and Eastern Europe and Asia, 502 patients with ERBB2–positive, early breast cancer were randomly assigned to receive neoadjuvant HD201 or trastuzumab for 8 cycles concurrent with 4 cycles of docetaxel, then 4 cycles of epirubicin and cyclophosphamide. Patients then had surgery followed by 10 cycles of adjuvant HD201 or trastuzumab.
After neoadjuvant treatment was given, the primary end point, total pathological complete response rate, was assessed when surgery was done. Equivalence was determined to have been met if the 95% confidence interval (CI) of the absolute difference in response rate between treatment arms in the patients treated per protocol was within the margin of +15%.
The researchers found that the total pathological complete response rate for the HD201 arm was 45%, and the rate for the trastuzumab arm was 48.7%. The −3.8% (95% CI, −12.8% to 5.4%) difference between these 2 arms was not significant and fell within the predefined equivalence margin. Moreover, the ratio of the response rates between the 2 arms was 0.92 (95% CI, 0.76 to 1.12).
Random assignment to treatment arms in TROIKA was stratified by tumor hormone receptor status, clinical stage, and recruitment region, and the baseline characteristics of the patients in the 2 arms were similar; 195 tumors (38.8%) were hormone receptor-negative, and 213 patients (42.4%) had Stage III disease.
During the entire period of treatment, 2232 treatment-emergent adverse events of special interest for trastuzumab were reported in 433 patients (86.1%). These events, which included cardiotoxic effects, infusion site reactions, hypersensitivity, hematotoxic effects, pulmonary disorders, and infections, were reported in 220 patients (88.0%) in the HD201 arm and 213 patients (84.5%) in the trastuzumab arm.
Analysis of study data was done on February 12, 2021, after the adjuvant phase of the study was completed at a median of 31 months (interquartile range, 28 to 33 months) of follow-up.
