On April 7, 2021, the U.S. Food and Drug Administration (FDA) granted regular approval to sacituzumab govitecan (Trodelvy®) for patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who received two or more prior systemic therapies, at least one of which for metastatic disease.
In April 2020, sacituzumab govitecan received accelerated approval for patients with mTNBC who received at least two prior therapies for metastatic disease. The April 2021 trial was confirmatory for the accelerated approval.
Efficacy and safety were evaluated in a multicenter, open-label, randomized trial (ASCENT; NCT02574455) of 529 patients with unresectable locally advanced or mTNBC who had relapsed after at least two prior chemotherapies, one of which could be in the neoadjuvant or adjuvant setting if progression occurred within 12 months. Patients were randomized 1:1 to receive either sacituzumab govitecan 10 mg/kg via IV infusion on days 1 and 8 of a 21-day cycle (n = 267) or physician’s choice of single-agent chemotherapy (n = 262).
The primary efficacy endpoint was progression-free survival (PFS) in patients without brain metastases at baseline as measured by a blinded independent centralized review and assessed using response evaluation criteria in solid tumors 1.1. Additional efficacy endpoints included PFS for the full population (with or without brain metastases) and overall survival (OS).
Among all randomized patients (with or without brain metastases), median PFS for patients receiving sacituzumab govitecan was 4.8 months (95% CI = 4.1, 5.8) compared to 1.7 months (95% CI = 1.5, 2.5) in those receiving chemotherapy (hazard ratio = 0.43; 95% CI = 0.35, 0.54; p < 0.0001). Median OS was 11.8 months (95% CI = 10.5, 13.8) and 6.9 months (95% CI = 5.9, 7.6), respectively (hazard ratio = 0.51; 95% CI: 0.41, 0.62; p < 0.0001).
The most common adverse reactions (> 25%) were nausea, neutropenia, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, rash, decreased appetite, and abdominal pain.
The recommended sacituzumab govitecan dose is 10 mg/kg once weekly on days 1 and 8 of 21-day treatment cycles until patients experience disease progression or unacceptable toxicity.
The review used the Real Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application six weeks ahead of its goal date.
FDA granted the application priority review and breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine or device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.