The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer

ESMO Open. 2022 Jun;7(3):100497. doi: 10.1016/j.esmoop.2022.100497. Epub 2022 May 25.

Abstract

Sacituzumab govitecan (SG) is an antineoplastic agent which combines a humanized monoclonal antibody binding to trophoblast cell surface antigen-2 (Trop-2)-expressing cancer cells, linked with cytotoxic moiety SN-38 (govitecan) with topoisomerase I inhibitor action. On 22 November 2021, a marketing authorization valid through the European Union (EU) was issued under the European Medicines Agency (EMA)'s accelerated assessment program for SG as monotherapy for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, including at least one of them for advanced disease. The assessment was based on results from an open-label, randomized, phase III trial to evaluate the safety, tolerability, pharmacokinetics and efficacy of SG versus treatment of physician's choice (TPC) in patients with mTNBC who received at least two prior treatments including at least one of them for advanced disease. The efficacy results in the overall population, based on mature data, showed a statistically significant improvement of SG over TPC in progression-free survival (PFS) and overall survival (OS). The median PFS was 4.8 months versus 1.7 months [hazard ratio (HR) = 0.43, n = 529; 95% CI 0.35-0.54; P < 0.0001] and the median OS was 11.8 months versus 6.9 months (HR = 0.51, n = 529; 95% CI 0.41-0.62; P < 0.0001). The most common (>30%) side effects of SG were diarrhea, neutropenia, nausea, fatigue, alopecia, anemia, constipation and vomiting. The aim of this manuscript is to summarize the scientific review of the application leading to regulatory approval in the EU.

Keywords: ADC; EMA; TNBC; Trop-2; sacituzumab govitecan.

Publication types

  • Review

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Agents* / adverse effects
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Humans
  • Immunoconjugates* / pharmacology
  • Immunoconjugates* / therapeutic use
  • Triple Negative Breast Neoplasms* / chemically induced
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Immunoconjugates
  • sacituzumab govitecan
  • Camptothecin