On February 3, 2023, the U.S. Food and Drug Administration (FDA) approved sacituzumab govitecan-hziy (Trodelvy®) for 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 two additional systemic therapies in the metastatic setting.

FDA Approves Sacituzumab Govitecan-Hziy for HR-Positive Breast Cancer

Efficacy was evaluated in TROPiCS-02 (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 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 their recurrence occurred within 12 months).

Patients were randomized 1:1 for sacituzumab govitecan-hziy 10 mg/kg via IV infusion on days 1 and 8 of a 21-day cycle (n = 272) or single-agent chemotherapy (n = 271). The investigator selected single-agent chemotherapy before randomization among eribulin (n = 130), vinorelbine (n = 63), gemcitabine (n = 56), or capecitabine (n = 22). Randomization was stratified by prior chemotherapy regimens for metastatic disease (2 versus 3–4), visceral metastasis (yes or no), and endocrine therapy in the metastatic setting for at least six months (yes or no). Patients were treated until they experienced disease progression or unacceptable toxicity.

The primary efficacy outcome measure was progression-free survival (PFS) determined by blinded independent central review per RECIST v1.1. A key secondary efficacy outcome measure was overall survival (OS). Median PFS was 5.5 months (95% CI = 4.2, 7.0) in the sacituzumab govitecan-hziy arm and 4 months (95% CI = 3.1, 4.4) in the single-agent chemotherapy arm (hazard ratio [HR] = 0.661 [95% CI = 0.529, 0.826]; p = 0.0003). Median OS was 14.4 months for those receiving sacituzumab govitecan-hziy (95% CI = 13.0, 15.7) and 11.2 months (95% CI = 10.1, 12.7) for those receiving single-agent chemotherapy (HR = 0.789 [95% CI = 0.646, 0.964]; p = 0.0200).

The most common adverse events reported in at least 25% of patients in the study treated with sacituzumab govitecan-hziy, 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%).

The recommended sacituzumab govitecan-hziy dose is 10 mg/kg administered via IV infusion once weekly on days 1 and 8 of 21-day treatment cycles until patients experience disease progression or unacceptable toxicity.

View the full prescribing information for sacituzumab govitecan-hziy.

The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.

The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.

The application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.