A trastuzumab biosimilar (HD201; Tuznue) demonstrated equivalence in efficacy and safety profiles compared with the reference product (Herceptin) in a phase 3 study of patients with erb-B2 receptor tyrosine kinase 2-positive (ERBB2+) breast cancer.

The randomized, double-blind, parallel-group, multicenter, international phase 3 clinical trial was published in JAMA Oncology and suggests that HD201 is just as effective at achieving total pathological complete response (tpCR) rates compared with the originator in patients with ERBB2+ breast cancer.

“These results support the application submitted for registration of HD201 as a biosimilar of trastuzumab,” the investigators wrote.

The European Medicines Agency has been reviewing Prestige Biopharma’s application for HD201 to receive marketing authorization since June 2019. If approved, it will compete against 6 other trastuzumab biosimilars and the originator product. Additionally, there are 5 FDA-approved trastuzumab biosimilars in the United States.

The TROIKA study was conducted across 70 centers in 12 countries throughout Western and Eastern Europe and Asia. For inclusion, patients had to be at least 18 years or older, have newly-diagnosed operable ERBB2+ early breast cancer, as well as adequate bone marrow, liver, and kidney functions.

Among the 502 patients that were included in the study, 251 were randomized to receive the biosimilar and 252 were assigned to receive the reference product. All patients received their respective drug intravenously every 3 weeks in a neoadjuvant setting for 8 cycles concurrently with 8 weeks of chemotherapy. Surgical procedures, including breast or axillary lymph node dissection, were performed within 3 to 8 weeks after the last trastuzumab dose. To collect data on cardiac safety and disease status, the patients attended an end-of-treatment visit 4 weeks after the last dose of the study therapy and were followed every 6 months for an additional 2 years or until death.

The study ended on February 12 , 2021, and has a median follow-up period of 31 months. The median age of the cohort was 54.1 years. By region, 7.8% of the patients were from Asia, 5.6% were from Western Europe, and 86.9% were from Eastern Europe.

The tpCR rates were 45.0% for the biosimilar treatment arm and 48.7% for the reference product arm. The difference in tpCR rates between the groups was nonsignificant and fell between the predefined equivalence margins (–3.8%; 95% CI, –12.8% to 5.4%). The tpCR rate ratio was 0.92 (95% CI, 0.76-1.12) between the treatment arms.

Overall, 2232 treatment-related adverse events were reported in 433 patients (86.1%), 220 of whom were in the biosimilar group (88.0%) and 213 in the reference product group (84.5%). Serious treatment-related adverse events were reported in 24 patients treated with the biosimilar and in 17 patients treated with the reference product. Treatment discontinuation occurred in 16 patients treated with HD201 and 12 treated with Herceptin.

The investigators said that interpretation of results may be limited because a direct relationship between survival outcomes and pCR early criteria of efficacy will need to be reported in future trials with a longer follow-up period.

“We are pleased to demonstrate HD201’s excellence through the Phase 3 study results published in JAMA Oncology….The company will accelerate global launch of Tuznue that can enhance affordability of trastuzumab to the patients in need,” said Lisa S. Park, CEO of Prestige BioPharma, in a statement.

Reference

Pivot X, Georgievich MA, Shamrai V, et al. Efficacy of HD201 vs referent trastuzumab in patients with ERBB2-positive breast cancer treated in the neoadjuvant setting: A multicenter phase 3 randomized clinical trial. JAMA Oncol. Published online March 03, 2022. doi:10.1001/jamaoncol.2021.8171