On February 3, the U.S. Food and Drug Administration (FDA) approved sacituzumab govitecan-hziy (Trodelvy) for patients with unresectable, locally advanced or metastatic, hormone receptor (HR)-positive, HER2-negative (immunohistochemistry [IHC] 0, IHC 1+, or IHC 2+ with a negative in situ hybridization test) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
Efficacy was evaluated in TROPiCS-02 (ClinicalTrials.gov identifier NCT03901339), a multicenter, open-label, randomized study of 543 patients with unresectable, locally advanced or metastatic, HR-positive, HER2-negative breast cancer whose disease progressed after the following in any setting: a CDK4/6 inhibitor, endocrine therapy, and a taxane. Patients received at least two prior chemotherapies in the metastatic setting (one of which could be in the neoadjuvant or adjuvant setting if recurrence occurred within 12 months).
Patients were randomly assigned 1:1 to receive sacituzumab govitecan at 10 mg/kg as an intravenous infusion on days 1 and 8 of a 21-day cycle (n = 272) or single-agent chemotherapy (n = 271). Single-agent chemotherapy was determined by the investigator before random assignment from one of the following choices: eribulin (n = 130), vinorelbine (n = 63), gemcitabine (n = 56), or capecitabine (n = 22). Random assignment was stratified by the following factors: prior chemotherapy regimens for metastatic disease (2 vs 3 or 4), visceral metastasis (yes or no), and endocrine therapy in the metastatic setting for at least 6 months (yes or no). Patients were treated until disease progression or unacceptable toxicity.
The primary efficacy outcome measure was progression-free survival as determined by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1; a key secondary efficacy outcome measure was overall survival.
Progression-Free and Overall Survival
Median progression-free survival was 5.5 months (95% confidence interval [CI] = 4.2–7.0 months) in the sacituzumab govitecan arm and 4 months (95% CI = 3.1–4.4 months) in the single-agent chemotherapy arm (hazard ratio [HR] = 0.661, 95% CI = 0.529–0.826, P = .0003). Median overall survival was 14.4 months for those receiving sacituzumab govitecan (95% CI = 13.0–15.7 months) and 11.2 months (95% CI = 10.1–12.7 months) for those receiving single-agent chemotherapy (HR = 0.789, 95% CI = 0.646–0.964, P = .0200).
The most common adverse events occurring in ≥ 25% of patients treated with sacituzumab govitecan in TROPiCS-02, 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%).
Hope S. Rugo, MD, FASCO
“Despite decades of advances, people living with pretreated HR-positive, HER2-negative 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,” said Hope S. Rugo, MD, FASCO, Professor of Medicine and Director, Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center, and principal investigator of the TROPiCS-02 study, in a press release from Gilead Sciences, Inc. “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 3 months with a quality-of-life benefit for these women is exceptional.”
The recommended sacituzumab govitecan dose is 10 mg/kg administered as an intravenous infusion once weekly on days 1 and 8 of 21-day treatment cycles until disease progression of unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment, and the application was granted Priority Review.