Oliva Andrea, Scavone Cristina, Riccardi Consiglia, Bernardi Francesca Futura, Salvo Francesco, Mascolo Annamaria
Eu2P Programme, University of Bordeaux, 146, rue Léo Saignat, 33076, Bordeaux, France.
Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Via Costantinopoli 16, 80138, Naples, Italy.
Clin Transl Oncol. 2025 Apr;27(4):1826-1838. doi: 10.1007/s12094-024-03642-x. Epub 2024 Sep 18.
In the last decade trastuzumab biosimilars became more and more frequent. Among their uses, from several years, they have been available in Europe for the treatment of HER2-positive metastatic breast cancer, as an alternative to Herceptin®.
METHODS/PATIENTS: This meta-analysis aimed to analyze the available literature with particular focus on phase 3 randomized clinical trials (RCTs) comparing adverse events between trastuzumab biosimilar and originator. A systematic review was conducted in Pubmed and Scopus to include all phase 3 RCTs related to trastuzumab in patients with HER2-positive breast cancer and published up to July 31, 2023. Of the 508 records identified, 14 articles were meta-analyzed for safety information, including serious treatment emergent adverse events, death-related adverse events, neutropenia, leukopenia, infections, increased ALT, increased AST, anti-drug antibody, and neutralizing antibody.
Included patients had an early breast cancer (N=2,877) or a metastatic breast cancer (N=2,603). No significant difference in death-related adverse events was found for trastuzumab biosimilar and originator when evaluated for an early breast cancer in the neoadjuvant phase (Risk Ratio [RR], 1.30; 95% confidence interval [CI], 0.47-3.59; I2 = 0%; p = 0.57) and overall (RR, 0.43; 95%CI, 0.11-1.66; I2 = 20%; p = 0.26), and for metastatic breast cancer (RR, 0.61; 95%CI, 0.30-1.26; I2 = 0%; p = 0.85).
No difference was also observed for all other safety outcomes as in accordance with clinical studies necessary for the registration and approval of a biosimilar at a European level.
在过去十年中，曲妥珠单抗生物类似药越来越常见。在其用途中，多年来在欧洲已可用于治疗HER2阳性转移性乳腺癌，作为赫赛汀®的替代药物。
方法/患者：本荟萃分析旨在分析现有文献，特别关注比较曲妥珠单抗生物类似药与原研药不良事件的3期随机临床试验（RCT）。在PubMed和Scopus中进行了系统评价，以纳入截至2023年7月31日发表的所有与HER2阳性乳腺癌患者曲妥珠单抗相关的3期RCT。在识别出的508条记录中，对14篇文章进行了安全性信息的荟萃分析，包括严重治疗突发不良事件、死亡相关不良事件、中性粒细胞减少、白细胞减少、感染、谷丙转氨酶升高、谷草转氨酶升高、抗药抗体和中和抗体。
纳入的患者患有早期乳腺癌（N = 2877）或转移性乳腺癌（N = 2603）。在新辅助阶段对早期乳腺癌进行评估时，曲妥珠单抗生物类似药与原研药在死亡相关不良事件方面未发现显著差异（风险比[RR]，1.30；95%置信区间[CI]，0.47 - 3.59；I² = 0%；p = 0.57），总体上也未发现显著差异（RR，0.43；95%CI，0.11 - 1.66；I² = 20%；p = 0.26），转移性乳腺癌患者中也未发现显著差异（RR，0.61；95%CI，0.30 - 1.26；I² = 0%；p = 0.85）。
对于所有其他安全性结果，也未观察到差异，这与欧洲层面生物类似药注册和批准所需的临床研究一致。
