Pharmacologie - Option pharmaco-épidémiologie, pharmaco-vigilance

• Evaluation of trastuzumab safety profile: analysis of ADRs occurred in the EU countries during years 2018-2024 after the availability of biosimilars

  by Andrea OLIVA (Bordeaux Population Health Research Center)

  The defense will take place the 12-05-2025 at 11h00 - En visioconférence

  in front of the jury composed of

  • Francesco SALVO - Professeur des universités - Université de Bordeaux - Directeur de these
  • Armando GENAZZANI - Professeur des universités - Università di Torino - Rapporteur
  • Annamaria DE LUCA - Professeure des universités - Università degli Studi di Bari Aldo Moro - Rapporteur
  • Paola MINGHETTI - Professeure des universités - Università degli studi di Milano - Examinateur
  • Marco TUCCORI - Associate Professor - Università di Verona - Examinateur
  • Cristina SCAVONE - Associate Professor - Link Campus University - CoDirecteur de these

  Summary

  In the last decade, cancer therapies have increasingly taken the form of combination treatments in which biologic agents play a crucial role. In breast cancer, the treatment strategy is adjusted to intrinsic subtypes such as human epidermal growth factor receptor-2(HER2)-positive. With the introduction of trastuzumab, a monoclonal antibody against HER2, survival has significantly improved in early and metastatic breast cancer. Considering that Herceptin has been on the European market for over twenty years and its biosimilars have also been available since 2018, through the evaluation of the scientific literature and safety information from post-marketing reports we want to carry out an updated evaluation of the safety profile of trastuzumab, with a secondary focus on the differences between the originator and the biosimilars. Specifically, two analyses were conducted: a meta-analysis of phase three randomized trials and an evaluation of Individual Case of Safety Reports (ICSRs) from EudraVigilance in the period 2018-2024. Through the literature screening were been identified 199 records then 42 articles were considered eligible according to inclusion criteria therefor analysed as full text. At the end 14 records are included for the meta-analysis; the outcome of our analysis showed that 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). From post-marketing analysis 11,951 ICSRs were collected, covering 29,726 PTs, related to trastuzumab products; during the study period, the majority of ICSRs reported trastuzumab originator as suspected drug. ICSRs were mainly classified as serious, especially for trastuzumab originator, and that the outcome was mostly reported as favorable, especially for biosimilars-related ADRs. For the SOC "Cardiac Disorders", originator trastuzumab was most frequently reported as a suspect drug, while for the SOC "Respiratory Disorders", originator was less frequently reported compared to biosimilars, as well as for infusion reactions. Analysis of data from the literature and post-marketing data confirmed the safety profile of trastuzumab, with no significant differences emerging between the originator and biosimilars.