HLX02 对比曲妥珠单抗用于治疗复发或转移性 HER2 阳性乳腺癌的疗效、安全性和免疫原性：一项随机 III 期等效性试验
Efficacy, Safety, and Immunogenicity of HLX02 Compared with Reference Trastuzumab in Patients with Recurrent or Metastatic HER2-Positive Breast Cancer: A Randomized Phase III Equivalence Trial.
机构信息
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.
Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
出版信息
BioDrugs. 2021 May;35(3):337-350. doi: 10.1007/s40259-021-00475-w. Epub 2021 Apr 7.
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 (ORR). 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 ORR 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).
背景
HLX02 是一种已获批的曲妥珠单抗生物类似药。
目的
本研究旨在评估 HLX02 对比参照曲妥珠单抗在人表皮生长因子受体 2（HER2）阳性复发性或转移性乳腺癌患者中的疗效、安全性和免疫原性。
患者和方法
这是一项在中国、菲律宾、波兰和乌克兰的 89 家中心开展的随机、双盲、III 期研究。符合条件的患者按 1:1 随机分配接受 HLX02 或欧盟（EU）来源的曲妥珠单抗（初始剂量 8mg/kg，随后每 3 周 6mg/kg，最多 12 个月）联合多西他赛静脉输注。主要终点为截至第 24 周的总缓解率（ORR）。如果差异的 95%置信区间（CI）在±13.5%内，则宣布等效。至少接受一剂研究药物的患者可评估安全性和免疫原性。
结果
2016 年 11 月 11 日至 2019 年 7 月 10 日，共纳入 649 例患者。HLX02 组（n=324）和 EU-曲妥珠单抗组（n=325）的 ORR 分别为 71.3%和 71.4%，差异为-0.1%（95%CI-7 至 6.9），完全在预设的等效区间内。所有次要疗效分析均未见统计学显著差异。HLX02 组和 EU-曲妥珠单抗组的安全性特征和免疫原性相似。两组各有 98.8%的患者至少发生 1 次治疗期间出现的不良事件（TEAE），23.8%和 24.9%的患者发生严重 TEAE，两组各有 0.6%的患者出现抗药物抗体。
结论
在 HER2 阳性复发性或转移性乳腺癌患者中，HLX02 显示出与参照曲妥珠单抗等效的疗效，且安全性和免疫原性相似。
临床试验注册
Chinadrugtrials.org CTR20160526（2016 年 9 月 12 日），ClinicalTrials.gov NCT03084237（2017 年 3 月 20 日），EudraCT 2016-000206-10（2017 年 4 月 27 日）。
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