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

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.

Figure 1

Kaplan–Meier estimates of PFS by IRC assessment per RECIST v1.1 in the ITT population (study IMMU-132-05). PFS is defined as the time from the date of randomization to the date of the first radiological disease progression or death due to any cause, whichever comes first. IRC, independent review committee; ITT, intention to treat; PFS, progression-free survival; RECIST, Response Evaluation Criteria in Solid Tumors; TPC, treatment of physician’s choice.

Figure 2

Kaplan–Meier plot of OS (ITT population). OS is defined as the time from date of randomization to the date of death from any cause. ITT, intention to treat; OS, overall survival; TPC, treatment of physician’s choice.