What is the role of Sacituzumab Govitecan (Trodelvy), a novel antibody-drug conjugate, in the treatment of Triple-Negative Breast Cancer (TNBC)?

From the Guidelines

Sacituzumab govitecan is the recommended treatment for patients with metastatic triple-negative breast cancer who have received at least two prior therapies for metastatic disease, due to its significant improvement in progression-free survival and overall survival compared to standard chemotherapy, as demonstrated in the ASCENT5 trial 1.

Mechanism of Action and Efficacy

The medication works through a dual mechanism, with the antibody component (sacituzumab) targeting the Trop-2 receptor commonly overexpressed in TNBC cells, and the drug payload (SN-38, an active metabolite of irinotecan) delivering potent chemotherapy directly to cancer cells. The ASCENT5 trial showed that sacituzumab govitecan improved PFS compared to standard therapy, with a median PFS of 5.6 months versus 1.7 months, and a hazard ratio of 0.41 (P < .0001) 1. Additionally, sacituzumab govitecan improved OS compared to standard therapy, with a median OS of 12.1 months versus 6.7 months, and a hazard ratio of 0.48 (P < .0001) 1.

Dosage and Administration

The recommended dose of sacituzumab govitecan is 10 mg/kg administered as an intravenous infusion on days 1 and 8 of 21-day treatment cycles, until disease progression or unacceptable toxicity occurs.

Safety and Monitoring

Common side effects of sacituzumab govitecan include neutropenia, diarrhea, nausea, fatigue, alopecia, anemia, and vomiting. Patients should receive anti-nausea medications before infusion and have complete blood counts monitored regularly. Healthcare providers should implement dose modifications for severe neutropenia, severe diarrhea, or other grade 3-4 toxicities.

Key Points

• Sacituzumab govitecan is an effective treatment for metastatic TNBC patients who have received at least two prior therapies for metastatic disease.
• The medication improves PFS and OS compared to standard chemotherapy.
• Common side effects include neutropenia, diarrhea, and nausea.
• Patients should receive regular monitoring and dose modifications as needed.

From the FDA Drug Label

TRODELVY is indicated for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. TRODELVY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Locally Advanced or Metastatic Breast Cancer Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. (1.1,14.1)

Sacituzumab Govitecan is a novel antibody-drug conjugate indicated for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease 2, 2, 2.

• The recommended dose is 10 mg/kg once weekly on Days 1 and 8 of continuous 21-day treatment cycles until disease progression or unacceptable toxicity.
• Key warnings include severe or life-threatening neutropenia and diarrhea.
• Patients should be monitored for infusion-related reactions and nausea/vomiting.

From the Research

Sacituzumab Govitecan Mechanism and Efficacy

• Sacituzumab govitecan is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan 3.
• The drug has shown promising anti-cancer activity in patients with metastatic triple-negative breast cancer (TNBC) previously treated with at least two prior lines of systemic therapy 3, 4.
• A Phase III randomized clinical trial demonstrated that sacituzumab govitecan significantly improved progression-free survival and overall survival compared to single-agent chemotherapy in patients with relapsed or refractory metastatic TNBC 5.

Safety and Tolerability

• The most common adverse events associated with sacituzumab govitecan are nausea, neutropenia, and diarrhea 3, 6, 4, 7, 5.
• Neutropenia is the most common serious treatment-related adverse event, with grade 3 or 4 neutropenia occurring in 21.0% and 8.7% of patients, respectively 6.
• Dose reductions and treatment discontinuation due to adverse events are common, with 51.3% of patients requiring dose reductions and 13.2% discontinuing treatment 7.

Real-World Clinical Outcomes

• Real-world studies have demonstrated that sacituzumab govitecan retains its clinical activity in heavily pretreated patients with metastatic TNBC, with an objective response rate of 27.8% and median overall survival of 9.6 months 7.
• The use of premedication and supportive measures can help manage the toxicity profile of sacituzumab govitecan, allowing for satisfactory treatment outcomes 6.
• Sequential use of antibody-drug conjugates, such as sacituzumab govitecan followed by trastuzumab deruxtecan, may be a viable treatment strategy for patients with HER2-low metastatic TNBC 7.