Updated efficacy and safety of HLX02 versus reference trastuzumab in metastatic HER2-positive breast cancer: A randomized phase III equivalence trial
Binghe Xu,
Qingyuan Zhang,
Tao Sun,
Wei Li,
Yue'e Teng,
Xichun Hu,
Igor Bondarenko,
Hryhoriy Adamchuk,
Liangming Zhang,
Dmytro Trukhin,
Shusen Wang,
Hong Zheng,
Zhongsheng Tong,
Yaroslav Shparyk,
Futang Yang,
Haoyu Yu,
Jing Li,
Qingyu Wang,
Jun Zhu
Affiliations
Binghe Xu
Department of Medical Oncology, National Cancer Center/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 100021, China; Corresponding author. Cancer Hospital Chinese Academy of Medical Sciences, No. 17, Panjiayuan Nanli, Beijing, 100021, China.
Qingyuan Zhang
Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
Tao Sun
Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Liaoning, China
Wei Li
Internal Medicine Oncology, The First Hospital of Jilin University, Jilin, China
Yue'e Teng
Internal Medicine Oncology, The First Hospital of China Medical University, Shenyang, China
Xichun Hu
Internal Medicine Oncology, Shanghai Cancer Hospital, Fudan University, Shanghai, China
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 (ORR24). 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).
