On April 22, the U.S. Food and Drug Administration (FDA) approved sacituzumab govitecan-hziy (Trodelvy) for the treatment of adult patients with metastatic triple-negative breast cancer who have received at least two prior therapies for metastatic disease.
Sacituzumab govitecan-hziy is the first antibody-drug conjugate approved by the FDA specifically for relapsed or refractory metastatic triple-negative metastatic breast cancer. It is also the first FDA-approved anti–Trop-2 antibody-drug conjugate. The agent is a Trop-2–directed antibody and topoisomerase inhibitor drug conjugate.
Richard Pazdur, MD
“Metastatic triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options. Chemotherapy has been the mainstay of treatment for triple-negative breast cancer. The approval of sacituzumab govitecan-hziy represents a new targeted therapy for patients living with this aggressive malignancy,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “There is intense interest in finding new medications to help treat metastatic triple-negative breast cancer. [This] approval provides patients who’ve already tried two prior therapies with a new option.”
The FDA approved sacituzumab govitecan-hziy based on the results of the phase II IMMU-132-01 clinical trial of 108 patients with metastatic triple-negative breast cancer who had received a range of 2 to 10 prior treatments for metastatic disease. Patients received sacituzumab govitecan-hziy at 10 mg/kg intravenously on days 1 and 8 every 21 days. Tumor imaging was obtained every 8 weeks, and patients were treated until disease progression or intolerance to therapy.
The efficacy of sacituzumab govitecan-hziy was based on the overall response rate. The overall response rate was 33.3% (95% confidence interval [CI] = 24.6%–43.1%), with a median duration of response of 7.7 months (95% CI = 4.9–10.8). Of the patients with a response to sacituzumab govitecan-hziy, 55.6% maintained their response for 6 or more months and 16.7% maintained their response for 12 or more months.
The most common reported side effects (occurring in 25% or more of patients) were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash, and abdominal pain. The most common grade 3 or 4 adverse events (occurring in more than 5% of patients) were neutropenia, white blood cell count decreased, anemia, hypophosphatemia, diarrhea, fatigue, nausea, and vomiting.
Two percent of patients discontinued treatment due to adverse events. There were no deaths related to treatment, and no severe cases of neuropathy or interstitial lung disease.
The prescribing information for sacituzumab govitecan-hziy includes a Boxed Warning to advise health-care professionals and patients about the risk of severe neutropenia and severe diarrhea.
Continued approval of sacituzumab govitecan-hziy may be contingent upon verification of clinical benefit in the confirmatory phase III ASCENT study, which was recently halted by the independent data safety monitoring committee for compelling evidence of efficacy across multiple endpoints.
The recommended sacituzumab govitecan-hziy dose is 10 mg/kg administered by intravenous infusion administered on days 1 and 8 every 21 days until disease progression or unacceptable toxicity.