The approval is based on results from the phase 3 TROPiCS-02 trial demonstrating overall and progression survival benefits with sacituzumab govitecan compared with physician’s choice of single-agent chemotherapy.
The FDA approved sacituzumab govitecan (Trodelvy) to treat patients with unresectable locally advanced or metastatic hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer following endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting.1
The approval is based on results from the phase 3 TROPiCS-02 trial (NCT03901339) demonstrating a statistically significant and clinically meaningful overall survival (OS) benefit with sacituzumab govitecan compared with physician’s choice of single-agent chemotherapy.2
A total of 543 patients were enrolled in the global, multicenter, open-label TROPiCS-02 study and randomized to receive either sacituzumab govitecan or physician's choice of single-agent chemotherapy with eribulin, capecitabine, gemcitabine, or vinorelbine. All patients had HR-positive, HER2-negative metastatic breast cancer and had undergone treatment with endocrine therapy, a CDK4/6 inhibitor, and 2 to 4 lines of chemotherapy for metastatic disease.
Patients treated with sacituzumab govitecan showed a median OS of 14.4 months (95% CI, 13.0-15.7), while patients treated with single-agent chemotherapy had a median OS of 11.2 months (95% CI, 10.1-12.7)—a 21% decrease in the risk of death among the sacituzumab govitecan cohort (HR, 0.79; 95% CI, 0.65-0.96; P = .02).
The median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan arm (95% CI, 4.2-7.0), while PFS in the chemotherapy arm was 4 months (95% CI, 3.1-4.4). The difference amounts to a 34% reduction in the risk of disease progression or death in the sacituzumab govitecan cohort (HR, 0.66; 95% CI, 0.53-0.83; P = .0003).
“Despite decades of advances, people living with pre-treated HR+/HER2- metastatic breast cancer need new treatment options. Nearly all people with this type of breast cancer will eventually develop resistance to endocrine-based therapies and progress on available chemotherapies,” Hope S. Rugo, MD, professor of medicine and director of Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center, said in a statement. “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.”
The primary end point in the study was PFS, and secondary end points included OS, overall response rate (ORR), clinical benefit rate, duration of response, assessment of tolerability and safety, and quality-of-life measures. The sacituzumab govitecan arm significantly improved ORR and time to deterioration of global health status, among other secondary end points. No new safety signals were identified in the study.
Sacituzumab govitecan was first FDA approved in April 2021 for the treatment of patients with unresectable, locally advanced or metastatic triple-negative breast cancer following 2 or more systemic therapies, at least 1 of them for metastatic disease.3
“We are pleased that Trodelvy could now provide new hope for people living with pre-treated HR+/HER2- metastatic breast cancer, building on the transformative role that Trodelvy is already playing for people with metastatic triple-negative breast cancer,” Daniel O'Day, chairman and chief executive officer of Gilead Sciences, said. “We thank the physicians, patients and their families who put their trust in the TROPiCS-02 study and helped make this milestone possible.”
1. US FDA approves Trodelvy in pre-treated HR+/HER2- metastatic breast cancer. News release. Gilead Sciences. February 3, 2023. Accessed February 3, 2023. https://www.gilead.com/news-and-press/press-room
2. Rugo HS, Bardia A, Marme F, et al. Overall survival (OS) results from the phase III TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician's choice (TPC) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC). Ann Oncol. 2022;33(suppl 7):S1386. doi:10.1016/j.annonc.2022.08.012
3. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. News release. FDA. April 7, 2021. Accessed February 3, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs