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Clinical Trial
. 2022 May 1;8(5):698-705.
doi: 10.1001/jamaoncol.2021.8171.

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

Xavier Pivot  1 , M A Georgievich  2 , Volodymyr Shamrai  3 , Giorgi Dzagnidze  4 , Hwoei Fen Soo Hoo  5 , Viriya Kaewkangsadan  6 , Fausto Petrelli  7 , Cristian Villanueva  8 , Lipatov O Nikolaevich  9 , Jocelyn Hii  10 , Jamie Kim  10 , Sumita Pradhan  10 , Litha Jaison  10 , Peggy Feyaerts  10 , Leonard Kaufman  11 , Marie-Paule Derde  11 , Ghislain M C Bonamy  10 , Filip Deforce  11 , David G Cox  1
Affiliations
Clinical Trial

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

Xavier Pivot et al. JAMA Oncol. .

Erratum in

  • Error in Author Surname.
    [No authors listed] [No authors listed] JAMA Oncol. 2022 May 1;8(5):784. doi: 10.1001/jamaoncol.2022.0909. JAMA Oncol. 2022. PMID: 35389424 Free PMC article. No abstract available.

Abstract

Importance: The drug HD201 is a biosimilar candidate for breast cancer treatment as the reference trastuzumab.

Objective: To compare the efficacy of HD201 with referent trastuzumab.

Design, setting, and participants: This randomized clinical trial (TROIKA) included 502 women with ERBB2-positive early breast cancer treated with either HD201 or referent trastuzumab. It was conducted across 70 centers in 12 countries, including Western and Eastern Europe and Asian countries. Randomization was stratified by tumor hormone receptor status, clinical stage, and geographic region of recruitment. This analysis was conducted on February 12, 2021, after the completion of the adjuvant phase at a median of 31 months (IQR, 28-33 months) of follow-up.

Interventions: Patients with ERBB2-positive early breast cancer were randomly assigned to receive HD201 or referent trastuzumab in the neoadjuvant setting for 8 cycles, concurrently with 4 cycles of docetaxel, which was followed by 4 cycles of epirubicin and cyclophosphamide. Patients then underwent surgery, which was followed by treatment with 10 cycles of adjuvant HD201 or referent trastuzumab.

Main outcome and measures: The primary end point was the total pathological complete response (tpCR) assessed after neoadjuvant treatment. Equivalence was concluded if the 95% CI of the absolute difference in tpCR between arms in the per-protocol set was within the margin of more or less than 15%. Other objectives included the breast pathological complete response, overall response, event-free and overall survival, safety, pharmacokinetics, and immunogenicity.

Results: A total of 502 female patients (mean [range] age, 53 [26-82] years) were randomized to receive either HD201 or referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. The baseline characteristics were well balanced between the 2 arms; 195 tumors (38.8%) were hormone receptor-negative , and 213 patients (42.4%) had clinical stage III disease. The tpCR rates were 45% and 48.7% for HD201 and referent trastuzumab, respectively. The difference between the 2 groups was not significant at -3.8% (95% CI, -12.8% to 5.4%) and fell within the predefined equivalence margins. The ratio of the tpCR rates between the 2 arms was 0.92 (95% CI, 0.76 to 1.12). A total of 433 patients (86.1%) presented with 2232 treatment-emergent adverse events of special interest for trastuzumab during the entire treatment period, with 220 (88.0%) and 213 (84.5%) patients in the HD201 and referent trastuzumab groups, respectively.

Conclusions and relevance: The results of this randomized clinical trial found that HD201 demonstrated equivalence to referent trastuzumab in terms of efficacy for the end point of tpCR, with a similar safety profile.

Trial registration: ClinicalTrials.gov Identifier: NCT03013504.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Pivot reported being an unpaid adviser for Prestige Biopharma. Dr Dzagnidze reported personal fees from Khechinashvili University Hospital during the conduct of the study. Dr Kaewkangsadan reported grants from Prestige BioPharma during the conduct of the study. Drs Derde, Kaufman, and Deforce are/were employees of DICE Ltd and had a memorandum of understanding with Prestige BioPharma Ltd. No other disclosures were reported.

Figures

Figure.
Figure.. CONSORT Flow Diagram Describing the Patient Distribution
FAS indicates full analysis set; mFAS, modified full analysis set.
See this image and copyright information in PMC

References

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    1. Pivot X, Deslypere JP, Park LS, Kim MJ, Lee W, Lee J. A randomized phase I study comparing the pharmacokinetics of HD201, a trastuzumab biosimilar, with European Union-sourced Herceptin. Clin Ther. 2018;40(3):396-405.e4. doi:10.1016/j.clinthera.2018.01.009 - DOI - PubMed
    1. Demarchi M, Coliat P, Shii Hii JC, et al. . TROIKA-1: a double-blind, randomized, parallel group study aimed to demonstrate the equivalent pharmacokinetic profile of HD201, a potential biosimilar candidate to trastuzumab, versus EU-Herceptin® and US-Herceptin® in healthy male subjects. Pharmacol Res Perspect. 2021;9(4):839-849. doi:10.1002/prp2.839 - DOI - PMC - PubMed

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