The Food and Drug Administration (FDA) has approved Trodelvy® (sacituzumab govitecan-hziy) for the treatment of adults with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting.
The approval was based on data from the phase 3 TROPiCS-02 study (ClinicalTrials.gov Identifier: NCT03901339), which included 543 patients with HR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitors and 2 to 4 lines of chemotherapy for metastatic disease. Patients were randomly assigned 1:1 to receive sacituzumab govitecan (n=272) or physician’s choice of chemotherapy (n=271): eribulin, capecitabine, gemcitabine, or vinorelbine.
Findings showed that treatment with sacituzumab govitecan reduced the risk of disease progression or death by 34% compared with chemotherapy (hazard ratio [HR], 0.661; 95% CI, 0.529-0.826; P =.0003). Median progression free survival (PFS) was 5.5 months (95% CI, 4.2-7.0) for the sacituzumab govitecan arm and 4 months (95% CI, 3.1-4.4) for the chemotherapy arm. Sacituzumab govitecan also demonstrated a statistically significant improvement in overall survival vs chemotherapy (14.4 months vs 11.2 months, respectively; HR, 0.789; 95% CI, 0.646-0.964; P =.0200).
Significant improvements with sacituzumab govitecan were observed in other secondary endpoints including objective response rate and time to deterioration assessed by the Global Health Status/Quality of Life and Fatigue scale per EORTC-QLQ-C30. In a post-hoc analysis, sacituzumab govitecan demonstrated efficacy across HER2-low and IHC0 status in pretreated metastatic breast cancer patients.
“Nearly all people with this type of breast cancer will eventually develop resistance to endocrine-based therapies and progress on available chemotherapies,” said Hope S. Rugo, MD, Professor of Medicine and Director, Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center, US and principal investigator of the TROPiCS-02 study. “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 most common adverse reactions reported with sacituzumab govitecan were diarrhea, febrile neutropenia, neutropenia, abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting. The most common grade 3-4 laboratory abnormalities were reduced neutrophils and leukocytes.
Trodelvy is also indicated for the treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer who have received 2 or more prior systemic therapies, at least 1 of them for metastatic disease.
US FDA approves Trodelvy® in pre-treated HR+/HER2- metastatic breast cancer. News release. Gilead Sciences, Inc. Accessed February 3, 2023. https://www.businesswire.com/news/home/20230131006182/en/U.S.-FDA-Approves-Trodelvy%C2%AE-in-Pre-treated-HRHER2–Metastatic-Breast-Cancer.