Sacituzumab Govitecan-Hziy Receives FDA Approval for the Treatment of Triple-Negative Breast Cancer

On 22 April 2020, the US Food and Drug Administration (FDA), for patients who had received at least two lines of therapy for metastatic disease and had triple-negative breast cancer, granted accelerated approval to sacituzumab govitecan-hziy (Trodelvy).

Breast cancer in which three receptors, the estrogen hormone receptor (ER), progesterone hormone receptor (PR) and human epidermal growth factor receptor 2 (HER2), are absent from the cell membrane is called triple-negative breast cancer. It accounts for approximately 15% of all breast cancers.

How Does Sacituzumab Govitecan-Hziy Work?

Cancer cells have a protein called Trop-2 that activates a calcium-dependent signaling pathway. Activation of Trop2 causes growth signals to be sent into the cell. Sacituzumab govitecan-hziy, considered a new targeted therapy for triple-negative breast cancer, was developed against this protein and is a drug consisting of an antibody-drug conjugate.

Sacituzumab, one of two conjugated drugs being investigated in this field, inhibits the Trop2 pathway and has received approval.

The IMMU-132-01 Study

The efficacy of sacituzumab govitecan-hziy was demonstrated in IMMU-132-01, a multicenter, single-arm study that enrolled 108 patients with metastatic triple-negative breast cancer (mTNBC) who had received at least two lines of therapy for metastatic disease. This study had previously been presented at the 2016 San Antonio Breast Cancer Symposium. Patients received 10 mg / kg of sacituzumab govitecan-hziy intravenously on days 1 and 8 of each 21-day cycle. Tumor imaging to assess treatment response was performed every 8 weeks, and patients were treated until disease progression or until they could no longer tolerate treatment because of side effects.

The primary efficacy outcome measure was overall response rate. The study measured an overall response rate of 33.3% (95% CI: 24.6, 43.1). Median duration of response was 7.7 months (95% CI: 4.9, 10.8).

The most common side effects (in ≥25% of patients) were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia (hair loss), constipation, rash, decreased appetite and abdominal pain. Sacituzumab govitecan-hziy can also cause severe neutropenia and diarrhea.

The recommended sacituzumab govitecan-hziy dose is 10 mg / kg, administered by intravenous infusion on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

Sacituzumab govitecan-hziy was granted accelerated approval for triple-negative breast cancer based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.