The Food and Drug Administration (FDA) has granted full approval to Trodelvy® (sacituzumab govitecan-hziy) for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received 2 or more prior systemic therapies, at least 1 of them for metastatic disease. The treatment had previously been granted accelerated approval for metastatic TNBC based on objective response rate and duration of response results in a phase 1/2 study.
Sacituzumab govitecan, a Trop-2-directed antibody and topoisomerase inhibitor conjugate, binds to Trop-2-expressing cancer cells and is internalized with the subsequent release of SN-38, the active metabolite of irinotecan. The resulting DNA damage leads to apoptosis and cell death.
The full approval was based on data from the multicenter, open-label, randomized phase 3 ASCENT study (ClinicalTrials.gov: NCT02574455), which assessed the efficacy and safety of sacituzumab govitecan in 529 patients with unresectable locally advanced or metastatic TNBC who had relapsed after 2 or more prior chemotherapies (1 of which could be in the neoadjuvant or adjuvant setting if progression occurred within a 12 month period).
Patients were randomly assigned 1:1 to receive either sacituzumab govitecan 10mg/kg as an intravenous infusion on days 1 and 8 of a 21-day cycle (n=267) or physician’s choice of single agent chemotherapy (n=262; eribulin [n=139], capecitabine [n=33], gemcitabine [n=38], or vinorelbine [n=52]).
The primary endpoint was progression-free survival (PFS) in patients without brain metastases at baseline. Key secondary endpoints included PFS for the full population (all patients with and without brain metastases) and overall survival (OS).
Results showed that among all patients, the median PFS was 4.8 months (95% CI, 4.1-5.8) in the sacituzumab govitecan arm compared with 1.7 months (95% CI, 1.5-2.5) in the chemotherapy arm (hazard ratio [HR] 0.43; 95% CI, 0.35-0.54; P <.0001). Median OS was 11.8 months (95% CI, 10.5-13.8) for patients treated with sacituzumab govitecan vs 6.9 months (95% CI, 5.9-7.6) for those who received chemotherapy (HR 0.51; 95% CI, 0.41-0.62; P <.0001).
In an exploratory analysis of patients with previously treated, stable brain metastases, the median PFS was 2.8 months (95% CI, 1.5-3.9) in the sacituzumab govitecan group compared with 1.6 months (95% CI, 1.3-2.9) in the chemotherapy group (stratified HR of 0.65; 95% CI, 0.35-1.22). The median OS was 6.8 months (95% CI, 4.7-14.1) and 7.4 months (95% CI, 4.7-11.1) in the sacituzumab govitecan and chemotherapy arms, respectively (stratified HR of 0.87; 95% CI, 0.47-1.63).
“Women with triple-negative breast cancer have historically had very few effective treatment options and faced a poor prognosis,” said Aditya Bardia, MD, MPH, Director of Breast Cancer Research Program, Mass General Cancer Center and Assistant Professor of Medicine at Harvard Medical School, and global principal investigator of the ASCENT study. “Today’s FDA approval reflects the statistically significant survival benefit seen in the landmark ASCENT study and positions sacituzumab govitecan-hziy as a potential standard of care for pre-treated TNBC.”
Trodelvy is supplied as 180mg lyophilized powder in single-dose vials. The product is not a substitute and should not be used with other drugs containing irinotecan or its active metabolite SN-38.
1. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. [press release]. Silver Spring, MD: US Food and Drug Administration; April 7, 2021.
2. FDA approves Trodelvy®, the first treatment for metastatic triple-negative breast cancer shown to improve progression-free survival and overall survival. [press release]. April 7, 2021.
3. Trodelvy [package insert]. Morris Plains, NJ: Immunomedics, Inc.; 2021.