From the Guidelines
Sacituzumab Govitecan is the recommended treatment option for patients with metastatic triple-negative breast cancer who have received at least two prior therapies, due to its significant improvement in progression-free survival and overall survival compared to standard therapy. This is based on the results of the ASCENT5 trial, which demonstrated a median progression-free survival of 5.6 months and a median overall survival of 12.1 months with sacituzumab govitecan, compared to 1.7 months and 6.7 months, respectively, with standard therapy 1. The drug's novel mechanism of action, which combines a Trop-2-targeting antibody with SN-38, a potent chemotherapy drug, allows for targeted delivery of chemotherapy to cancer cells, potentially improving efficacy while reducing systemic toxicity.
Key Benefits and Side Effects
The benefits of sacituzumab govitecan include:
- Improved progression-free survival and overall survival compared to standard therapy
- Targeted delivery of chemotherapy to cancer cells, potentially reducing systemic toxicity
- A new treatment option for patients who have progressed on standard therapies The common side effects of sacituzumab govitecan include:
- Neutropenia (51% vs 33% with standard therapy)
- Diarrhea (10% vs 1% with standard therapy)
- Leukopenia (10% vs 5% with standard therapy)
- Anemia (8% vs 5% with standard therapy)
- Febrile neutropenia (6% vs 2% with standard therapy)
Clinical Implications
The use of sacituzumab govitecan in the treatment of metastatic triple-negative breast cancer represents a significant advance in the management of this challenging cancer subtype. Its targeted nature and improved efficacy make it a valuable addition to the treatment arsenal for patients who have received at least two prior therapies. As with any chemotherapy agent, close monitoring for side effects, particularly neutropenia and diarrhea, is essential to ensure safe and effective treatment 1.
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.
The role of Sacituzumab Govitecan (Trodelvy, Sacituzumab) in the treatment of Triple-Negative Breast Cancer (TNBC) is as a treatment option for adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease 2.
- Key Points:
- Indicated for adult patients with unresectable locally advanced or metastatic TNBC
- Patients should have received two or more prior systemic therapies, with at least one for metastatic disease
- Sacituzumab govitecan-hziy is a Trop-2-directed antibody-drug conjugate that binds to Trop-2-expressing cancer cells and releases SN-38, a topoisomerase I inhibitor, leading to apoptosis and cell death 2 2
From the Research
Role of Sacituzumab Govitecan in TNBC Treatment
- Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate approved for patients with metastatic triple-negative breast cancer (mTNBC) who have received ≥2 prior systemic therapies 3, 4.
- The drug has shown promising anti-cancer activity in patients with mTNBC previously treated with at least two prior lines of systemic therapy 4, 5.
- SG has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea 3, 4, 6, 5.
Mechanism of Action
- SG is composed of SN-38 (a topoisomerase I inhibitor derived from irinotecan) covalently linked to an anti-Trop-2 monoclonal antibody (sacituzumab; hRS7) via a hydrolysable CL2A linker 7.
- The drug delivers therapeutic SN-38 concentration to Trop-2+ expressing tumor cells via rapid internalization and efficient payload release, inducing DNA breakage and inhibiting nucleic acid synthesis 7.
Clinical Outcomes
- The objective response rate (ORR) for SG in patients with mTNBC was 33.3% (36/108; 95% confidence interval, 24.6-43.1), and the median duration of response (DoR) among responders was 7.7 months (95% CI, 4.9-10.8) 4.
- The model-predicted proportions of patients with complete response (CR) and ORR at 10 mg/kg were 4.26% and 32.6%, respectively 3.
- Higher average concentration over the treatment duration for SG (CAVGSG) was the best predictor of CR and ORR, and higher CAVG for total antibody was the best predictor of overall survival (OS) and progression-free survival (PFS) 3.