The FDA has granted approval to sacituzumab govitecan-hziy (Trodelvy®, Gilead Sciences, Inc.) for treatment of unresectable, locally advanced, or metastatic hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer. Patients are required to have received at least one prior line of endocrine therapy and two systemic therapies in the metastatic setting.
"Sacituzumab govitecan is a first-in-class trophoblast cell-surface antigen 2 (Trop-2)–directed antibody-drug conjugate (ADC), consisting of a humanized anti–Trop-2 monoclonal antibody conjugated to the active metabolite of irinotecan, SN-38, via a hydrolyzable CL2A linker," wrote Hope Rugo, MD, Professor of Medicine at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, and colleagues in their published results of the TROPiCS-02 trial (NCT03901339), on which approval was based. "Because SN-38 is a membrane-permeable free molecule released in the tumor microenvironment, it may elicit antitumor effects in adjacent non–Trop-2-expressing tumor cells (bystander effect)."
Safety and efficacy were evaluated in the phase 3, multicenter, open-label trial in which 543 patients were randomized 1:1 to receive either 10 mg/kg of sacituzumab govitecan-hziy via intravenous infusion on Days 1 and 8 of a 21-day cycle, or an investigator-determined single-agent chemotherapy consisting of eribulin, vinorelbine, gemcitabine, or capecitabine. Stratification was based on number of prior chemotherapy regimens received in the metastatic setting, visceral metastasis, and endocrine therapy in the metastatic setting for at least six months. Patients in both arms were treated until disease progression or unacceptable toxicity.
The primary end point measured was progression-free survival as assessed by a blinded independent review committee (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, with a secondary end point of overall survival. The median progression-free survival in the sacituzumab govitecan-hziy arm was 5.5 months compared with 4 months in the single-agent chemotherapy arm. The median overall survival in the sacituzumab govitecan-hziy arm was 14.4 months compared with 11.2 months in the single-agent chemotherapy arm.
The most common adverse events in ≥25% of patients, including laboratory abnormalities, were decreased leukocyte count (88%), decreased neutrophil count (83%), decreased hemoglobin (73%), decreased lymphocyte count (65%), diarrhea (62%), fatigue (60%), nausea (59%), alopecia (48%), increased glucose (37%), constipation (34%), and decreased albumin (32%).
"Sacituzumab govitecan-hziy is a Trop-2–directed ADC that demonstrated significant clinical benefit and manageable safety compared with standard chemotherapy in a phase 3 trial of patients with unresectable locally advanced or metastatic, heavily pretreated, endocrine-resistant HR-positive/HER2-negative breast cancer, a population with limited treatment options," concluded Dr. Rugo and colleagues in their published results. "In accordance with the National Comprehensive Cancer Network (NCCN) Guidelines for Breast Cancer, sacituzumab govitecan-hziy is a preferred therapy option for patients with HR-positive/HER2-negative cancers after prior treatment including endocrine therapy, a CDK4/6 inhibitor, and at least two lines of chemotherapy (including a taxane) for advanced breast cancer."
The recommended dosage is 10 mg/kg of sacituzumab govitecan-hziy as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles until disease progression or unacceptable toxicity.
For More Information
Rugo HS, Bardia A, Marmé F, et al (2022). Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol, 10;40(29):3365-3376. DOI:10.1200/JCO.22.01002
Clinicaltrials.gov (2022). Study of sacituzumab govitecan-hziy versus treatment of physician's choice in participants with HR+/HER2-metastatic breast cancer (TROPiCS-02). NLM identifier: NCT03901339.
Trodelvy® (sacituzumab govitecan-hziy) prescribing information (2023). Gilead Sciences. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761115s035lbl.pdf
US Food and Drug Administration (2023). FDA approves sacituzumab govitecan-hziy for HR-positive breast cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-hr-positive-breast-cancer
Image credit: National Cancer Institute. Licensed under the public domain.
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