Phase 3 TROIKA Results Demonstrate Clinical Similarity Between HD201 and Trastuzumab Reference in HER2-Positive Early Breast Cancer

2020 Year in Review - Biosimilars —January 13, 2021

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Biosimilars

Interim results from the phase 3 TROIKA trial demonstrate clinical equivalence between the biosimilar HD201 and trastuzumab reference in terms of efficacy, safety, pharmacokinetics, and immunogenicity in patients with HER2-positive early breast cancer.

At the European Society for Medical Oncology Virtual Congress 2020, the results of the TROIKA trial, a randomized, double-blind, parallel-group, multicenter phase 3 study that compared the efficacy, safety, pharmacokinetics, and immunogenicity of the proposed trastuzumab biosimilar HD201 compared with trastuzumab reference in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, were presented.

Eligible patients were randomized 1:1 to receive HD201 or trastuzumab reference as neoadjuvant therapy for 8 cycles in combination with chemotherapy; chemotherapy consisted of 4 cycles of docetaxel followed by 4 cycles of epirubicin + cyclophosphamide. Following surgery, patients received 10 cycles of HD201 or trastuzumab reference monotherapy as adjuvant therapy for up to 30 weeks. The primary end point was total pathologic complete response (tpCR) rate after neoadjuvant therapy and surgery up to 30 weeks; secondary end points included breast pathologic complete response (bpCR), overall response rate, event-free survival, pharmacokinetics, immunogenicity, and safety.

A total of 503 patients with HER2-positive early breast cancer were enrolled in the study; of these, 238 patients were treated with HD201 and 236 patients with trastuzumab reference, and were included in the per-protocol analysis group and evaluated for efficacy.

In the per-protocol population, the tpCR rates were similar between the groups (HD201, 46.60%; trastuzumab reference, 46.20%); equivalence between HD201 and trastuzumab reference was established, as the between-group difference in tpCR rate was 0.50% (95% confidence interval [CI], –8.6%-9.6%), with the 95% CIs contained within the predefined equivalence margins (–15%; 15%). The bpCR rate was 55.00% in the HD201 group and 53.40% in the trastuzumab reference group; the overall response rate was 90.80% and 89.40%, respectively.

The safety analysis included 250 patients in the HD201 group and 252 patients in the trastuzumab reference group. During the neoadjuvant phase, safety profiles among the groups were similar in terms of treatment-emergent adverse events (TEAEs; HD201, 96.4%; trastuzumab reference, 95.6%), serious TEAEs (HD201, 5.6%; trastuzumab reference, 4.4%), and TEAEs grade ≥3 (HD201, 29.2%; trastuzumab reference, 25.0%). Common TEAEs of any grade occurring in ≥10% of patients included alopecia, asthenia, nausea, diarrhea, stomatitis, and arthralgia. With regard to immunogenicity, the incidence of antidrug antibodies developed in the HD201 and trastuzumab reference groups was comparable.

At the onset of cycle 8, the mean steady-state Ctrough level in the HD201 group was 53.72 µg/mL in the HD201 group and 51.64 µg/mL in the trastuzumab reference group. The mean relative between-group difference was 4.0% [–2.6%; 10.6%], which was contained within the prespecified interval [–20%; 20%]; therefore, PK equivalence was established.

Interim results from the TROIKA trial demonstrate equivalence between HD201 and trastuzumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity in patients with HER2-positive early breast cancer.

Reference
Xavier P, et al. ESMO 2020. Abstract 166MO.

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Last modified: January 13, 2021

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