Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer

Abstract

PURPOSE Hormone receptor–positive (HR+) human epidermal growth factor receptor 2–negative (HER2–) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer. METHODS In this global, randomized, phase III study, SG was compared with physician's choice chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in endocrine-resistant, chemotherapy-treated HR+/HER2– locally recurrent inoperable or metastatic breast cancer. The primary end point was progression-free survival (PFS) by blinded independent central review. RESULTS Patients were randomly assigned to receive SG (n = 272) or chemotherapy (n = 271). The median age was 56 years, 95% had visceral metastases, and 99% had a prior cyclin-dependent kinase 4/6 inhibitor, with three median lines of chemotherapy for advanced disease. Primary end point was met with a 34% reduction in risk of progression or death (hazard ratio, 0.66 [95% CI, 0.53 to 0.83; P = .0003]). The median PFS was 5.5 months (95% CI, 4.2 to 7.0) with SG and 4.0 months (95% CI, 3.1 to 4.4) with chemotherapy; the PFS at 6 and 12 months was 46% (95% CI, 39 to 53) v 30% (95% CI, 24 to 37) and 21% (95% CI, 15 to 28) v 7% (95% CI, 3 to 14), respectively. Median overall survival (first planned interim analysis) was not yet mature (hazard ratio, 0.84; P = .14). Key grade ≥ 3 treatment-related adverse events (SG v chemotherapy) were neutropenia (51% v 38%) and diarrhea (9% v 1%). CONCLUSION SG demonstrated statistically significant PFS benefit over chemotherapy, with a manageable safety profile in patients with heavily pretreated, endocrine-resistant HR+/HER2– advanced breast cancer and limited treatment options.

Chemotherapy and Targeted Therapy for Endocrine-Pretreated or Hormone Receptor–Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update

“…No additional randomized controlled trials were identified. The original guideline Expert Panel was reconvened to review new evidence from TROPiCS-02 3 and to review and approve the revised recommendation.…”

“…1 That guideline was updated in August 2022 to incorporate the results of the DESTINY-Breast04 trial. 2 The results of the TROPiCS-02 3 trial, published on October 10, 2022, provided another signal to update.…”

HER2-low expression in breast oncology: treatment implications in the smart chemotherapy era

“…Moreover, the payloads carried by the two ADCs have specular pharmacodynamic proprieties: both the deruxtecan (exatecan derivative, for T-DXd) and SN-38 (active metabolite of irinotecan, for sacituzumab govitecan) bind to topoisomerase I-DNA cleavable complexes and stabilize them, resulting in the induction of double-strand DNA breaks and apoptosis (Pommier, 2006;Starodub et al, 2015;Ogitani et al, 2016). Further studies are needed in order to understand whether ADCs carrying similar payloads could be used in sequence (Modi et al, 2022;Rugo et al, 2022b).…”

Sacituzumab Govitecan in Hormone Receptor–Positive Metastatic Breast Cancer

“…The TROPiCS-02 trial in the article by Rugo et al 1 reported an improvement in progression-free survival of 1.5 months with sacituzumab govitecan, as compared with physician's choice of chemotherapy (5 v 4.4 months; hazard ratio, 0.66; 95% CI, 0.53 to 0.83), in advanced hormone receptor-positive breast cancer after two lines of therapy. This study population has great importance as they are heavily pretreated and have mostly exhausted of further lines of therapy.…”