Updated efficacy and safety of HLX02 versus reference trastuzumab in metastatic HER2-positive breast cancer: A randomized phase III equivalence trial.

Aim: Equivalence between HLX02 and trastuzumab sourced from the European Union (EU-trastuzumab), in combination with docetaxel, was demonstrated in a phase III study. This study aimed to evaluate the long-term efficacy and safety data after 3 years of follow-up.
Methods: Patients with previously untreated, HER2-positive metastatic breast cancer received intravenous HLX02 or EU-trastuzumab (initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for up to 12 months) in combination with docetaxel. Primary endpoint was the overall response rate up to week 24 (ORR ₂₄ ). Secondary endpoints including updated overall survival (OS), progression-free survival (PFS), safety and immunogenicity are reported in this long-term follow-up analysis.
Results: After a median follow-up duration of 35.0 months, 270 out of the 649 enrolled patients had died; 128 (39.5 %) in the HLX02 and 142 (43.7 %) in the EU-trastuzumab group. Median OS was 37.3 (95 % CI 36.2, not evaluable [NE]) months and not reached (95 % CI 34.2, NE) (stratified HR 0.86 [95 % CI 0.68, 1.10]; p = 0.229), with a 3-year OS rate of 57.5 % and 54.0 %, respectively. Median PFS at this long-term follow-up assessment was 11.7 (95 % CI 11.5, 12.1) months for the HLX02 group and 10.6 (95 % CI 9.5, 11.7) months for the EU-trastuzumab group (stratified HR 0.86 [95 % CI 0.69, 1.06]; p = 0.158). No new safety concerns were reported until the end of the survival follow-up.
Conclusion: Long-term efficacy and safety were consistent with the previous findings. No clinically meaningful differences between HLX02 and reference trastuzumab were demonstrated.
Clinical Trial Registration: Chinadrugtrials.org CTR20160526 (September 12, 2016), ClinicalTrials.gov NCT03084237 (March 20, 2017), EudraCT 2016-000206-10 (April 27, 2017).
Competing Interests: Declaration of competing interest Futang Yang, Haoyu Yu, Jing Li, Qingyu Wang and Jun Zhu are employees of Shanghai Henlius Biotech, Inc. All other authors have no competing interests to declare.
(Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)