Binghe Xu1, Qingyuan Zhang2, Tao Sun3, Wei Li4, Yue'e Teng5, Xichun Hu6, Igor Bondarenko7, Hryhoriy Adamchuk8, Liangming Zhang9, Dmytro Trukhin10, Shusen Wang11, Hong Zheng12, Zhongsheng Tong13, Yaroslav Shparyk14, Qingyu Wang15. 1. 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. xubinghe@medmail.com.cn. 2. Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China. 3. Internal Medicine Oncology, Liaoning Cancer Hospital, Liaoning, China. 4. Internal Medicine Oncology, The First Hospital of Jilin University, Jilin, China. 5. Internal Medicine Oncology, The First Hospital of China Medical University, Shenyang, China. 6. Internal Medicine Oncology, Shanghai Cancer Hospital, Fudan University, Shanghai, China. 7. Chemotherapy Department, Communal Institution Dnipropetrovsk City Multifield Clinical Hospital, Dnipro, Ukraine. 8. Chemotherapy Department, Communal Institution Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council, Kryvyi Rih, Ukraine. 9. Internal Medicine Oncology, Yantai Yuhuangding Hospital, Yantai, Shandong, China. 10. Daystay Care of Dispensary and Policlinic Department, Communal Institution Odesa Regional Oncological Dispensary, Odesa, Ukraine. 11. Internal Medicine Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou, China. 12. Internal Medicine Oncology, West China Hospital, Sichuan University, Sichuan, China. 13. Internal Medicine Oncology, Tianjin Cancer Hospital, Tianjin, China. 14. CI of LRC Lviv Oncological Regional Treatment and Diagnostic Center, Lviv, Ukraine. 15. Shanghai Henlius Biotech, Inc., Shanghai, China.
Abstract
BACKGROUND:HLX02 is an approved biosimilar of trastuzumab. OBJECTIVE: This study aimed to evaluated the efficacy, safety, and immunogenicity of HLX02 compared with reference trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer. PATIENTS AND METHODS: This randomized, double-blind, phase III study was conducted at 89 centers in China, the Philippines, Poland, and Ukraine. Eligible patients were randomized (1:1) to receive HLX02 or European Union (EU)-sourced trastuzumab (initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for up to 12 months) in combination with docetaxel intravenously. The primary endpoint was overall response rate up to week 24 (ORR24). Equivalence was declared if the 95% confidence interval (CI) of difference was within ± 13.5%. Safety and immunogenicity were evaluated in patients who received at least one dose of study medication. RESULTS:Between 11 November 2016 and 10 July 2019, a total of 649 patients were enrolled. The ORR24 was 71.3 and 71.4% in the HLX02 (n = 324) and EU-trastuzumab (n = 325) groups, with a difference of - 0.1% (95% CI - 7 to 6.9), which fell entirely in the predefined equivalence margins. No statistically significant differences were observed in all secondary efficacy analyses. Safety profiles and immunogenicity were comparable in HLX02 and EU-trastuzumab groups. In total, 98.8% of patients in each group experienced at least one treatment-emergent adverse event (TEAE), 23.8 and 24.9% experienced serious TEAEs, and 0.6% in each group had antidrug antibodies. CONCLUSIONS: Among patients with HER2-positive recurrent or metastatic breast cancer, HLX02 demonstrated equivalent efficacy and similar safety and immunogenicity to reference trastuzumab. CLINICAL TRIAL REGISTRATION: Chinadrugtrials.org CTR20160526 (12 September 2016), ClinicalTrials.gov NCT03084237 (20 March 2017), EudraCT 2016-000206-10 (27 April 2017).
RCT Entities:
BACKGROUND:HLX02 is an approved biosimilar of trastuzumab. OBJECTIVE: This study aimed to evaluated the efficacy, safety, and immunogenicity of HLX02 compared with reference trastuzumab in patients with humanepidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer. PATIENTS AND METHODS: This randomized, double-blind, phase III study was conducted at 89 centers in China, the Philippines, Poland, and Ukraine. Eligible patients were randomized (1:1) to receive HLX02 or European Union (EU)-sourced trastuzumab (initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for up to 12 months) in combination with docetaxel intravenously. The primary endpoint was overall response rate up to week 24 (ORR24). Equivalence was declared if the 95% confidence interval (CI) of difference was within ± 13.5%. Safety and immunogenicity were evaluated in patients who received at least one dose of study medication. RESULTS: Between 11 November 2016 and 10 July 2019, a total of 649 patients were enrolled. The ORR24 was 71.3 and 71.4% in the HLX02 (n = 324) and EU-trastuzumab (n = 325) groups, with a difference of - 0.1% (95% CI - 7 to 6.9), which fell entirely in the predefined equivalence margins. No statistically significant differences were observed in all secondary efficacy analyses. Safety profiles and immunogenicity were comparable in HLX02 and EU-trastuzumab groups. In total, 98.8% of patients in each group experienced at least one treatment-emergent adverse event (TEAE), 23.8 and 24.9% experienced serious TEAEs, and 0.6% in each group had antidrug antibodies. CONCLUSIONS: Among patients with HER2-positive recurrent or metastatic breast cancer, HLX02 demonstrated equivalent efficacy and similar safety and immunogenicity to reference trastuzumab. CLINICAL TRIAL REGISTRATION: Chinadrugtrials.org CTR20160526 (12 September 2016), ClinicalTrials.gov NCT03084237 (20 March 2017), EudraCT 2016-000206-10 (27 April 2017).
Authors: D J Slamon; B Leyland-Jones; S Shak; H Fuchs; V Paton; A Bajamonde; T Fleming; W Eiermann; J Wolter; M Pegram; J Baselga; L Norton Journal: N Engl J Med Date: 2001-03-15 Impact factor: 91.245
Authors: Giampietro Gasparini; Massimo Gion; Luigi Mariani; Paola Papaldo; Diana Crivellari; Gianfranco Filippelli; Alessandro Morabito; Vittorio Silingardi; Francesco Torino; Antonella Spada; Matelda Zancan; Livia De Sio; Antonio Caputo; Francesco Cognetti; Antonio Lambiase; Dino Amadori Journal: Breast Cancer Res Treat Date: 2006-07-19 Impact factor: 4.872
Authors: Michel Marty; Francesco Cognetti; Dominique Maraninchi; Ray Snyder; Louis Mauriac; Michèle Tubiana-Hulin; Stephen Chan; David Grimes; Antonio Antón; Ana Lluch; John Kennedy; Kenneth O'Byrne; PierFranco Conte; Michael Green; Carol Ward; Karen Mayne; Jean-Marc Extra Journal: J Clin Oncol Date: 2005-05-23 Impact factor: 44.544
Authors: Kathleen A Cronin; Linda C Harlan; Kevin W Dodd; Jeffrey S Abrams; Rachel Ballard-Barbash Journal: Cancer Invest Date: 2010-11 Impact factor: 2.176
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702