On February 3, 2023, the FDA approved a new indication for sacituzumab govitecan-hziy (Trodelvy; Gilead Sciences), a Trop-2–directed antibody–drug conjugate (ADC), in patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (immunohistochemistry [IHC] 0, IHC 1+, or IHC 2+/in situ hybridization–) breast cancer who have received endocrine-based therapy and ≥2 additional systemic therapies for metastatic disease. The FDA granted this application priority review.
The National Comprehensive Cancer Network now recommends sacituzumab govitecan as a category 1, preferred treatment for metastatic HR-positive, HER2-negative breast cancer, as defined in their Clinical Practice Guidelines in Oncology for breast cancer.
Sacituzumab govitecan was previously approved for the treatment of patients with locally advanced or metastatic urothelial cancer who previously received platinum-containing chemotherapy and a PD-1 or a PD-L1 inhibitor and for the treatment of patients with unresectable or metastatic triple-negative breast cancer who previously received ≥2 systemic therapies (≥1 for metastatic disease).
This FDA approval was based on the results of the phase 3 TROPiCS-02 study (NCT03901339), a multicenter, open-label, randomized, clinical trial of 543 patients with unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer that progressed after receiving, in any setting, a CDK4/6 inhibitor, endocrine therapy, and a taxane. Patients received ≥2 previous chemotherapies for metastatic disease (one of which could be neoadjuvant or adjuvant if the disease recurred within 12 months).
Patients were randomly assigned (1:1) to intravenous sacituzumab govitecan 10 mg/kg of body weight, on days 1 and 8 of a 21-day cycle, or to single-agent chemotherapy (chosen by the investigator before randomization from either eribulin, vinorelbine, gemcitabine, or capecitabine). Randomization was stratified by number of previous chemotherapy regimens for metastatic disease (2 vs 3 or 4), presence of visceral metastasis, and whether the patients received endocrine therapy in the metastatic setting for ≥6 months. Treatment continued until disease progression or unacceptable toxicity.
Progression-free survival (PFS) was the primary efficacy measure, and overall survival (OS) was among the secondary measures. The median PFS was 5.5 months (95% confidence interval [CI], 4.2-7.0) among patients who received sacituzumab govitecan and 4 months (95% CI, 3.1-4.4) among those who received single-agent chemotherapy (hazard ratio, 0.661; 95% CI, 0.529-0.826; P = .0003). In patients receiving sacituzumab govitecan, the median OS was 14.4 months (95% CI, 13.0-15.7), and it was 11.2 months (95% CI, 10.1-12.7) in patients receiving single-agent chemotherapy (hazard ratio, 0.789; 95% CI, 0.646-0.964; P = .02). This is the first OS benefit shown by a Trop-2–directed ADC in patients with HR-positive, HER2-negative metastatic breast cancer who received previous endocrine-based therapy and ≥2 chemotherapies.
The most common (≥25%) adverse events with sacituzumab govitecan in this study were decreased leukocyte count, decreased neutrophil count, decreased hemoglobin, decreased lymphocyte count, diarrhea, fatigue, nausea, alopecia, increased glucose, constipation, and decreased albumin.
“This approval is significant for the breast cancer community. We have had limited options to offer patients after endocrine-based therapy and chemotherapy, and to see a clinically meaningful survival benefit of more than three months with a quality-of-life benefit for these women is exceptional,” said principal trial investigator Hope S. Rugo, MD, Director of Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
The recommended dose of sacituzumab govitecan-hziy is 10 mg/kg administered as an intravenous infusion once weekly on days 1 and 8 of 21-day treatment cycles until disease progression or unacceptable toxicity.