Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: An Overview of Clinical Management and Potential Toxicities

Triple-negative breast cancer (TNBC) is a highly metastasized, heterogenous disease that represents approximately 10% to 15% of all breast cancers.¹ It has a poor prognosis and high relapse rate compared with non-TNBCs.² New therapies for TNBC have been desperately needed.² In April 2020, the US Food and Drug Administration granted accelerated approval to sacituzumab govitecan-hziy for treatment of patients with metastatic TNBC in patients who have received ≥2 previous therapies for metastatic diseases.³ Approval was based on data from the phase 1/2 IMMU-132-01 trial of sacituzumab govitecan.³

Sacituzumab govitecan is a novel antibody–drug conjugate composed of the active metabolite of irinotecan (SN-38) conjugated to a monoclonal antibody targeting Trop-2, an epithelial cell surface antigen overexpressed in many cancers.¹ Antibody–drug conjugates work by attaching to a specific receptor on the cancer cell and then delivering a small molecule. For sacituzumab govitecan, it is the active metabolite, irinotecan (SN-38), which is toxic to the cancer cell. Because SN-38 is delivered directly to the cancer cell, it is more effective than when given alone and with fewer side effects.¹

As a result of the rapid approval of sacituzumab govitecan, little data exist on the side-effect management needed to maximize the dose and duration of effective therapy while maintaining quality of life.¹ Sacituzumab govitecan has a defined and manageable toxicity profile, and early recognition and proactive management will allow clinicians to optimize treatment for patients.¹ The most common adverse reactions occurring in ≥25% of patients receiving sacituzumab govitecan include nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain.³

A number of sacituzumab govitecan side effects can be managed with simple interventions. Nausea, vomiting, and diarrhea can be managed with oral antiemetics, oral rehydration therapy, and opiates as required. More severe side effects like neutropenia will need to be managed alongside the patient’s physician and may warrant dose reduction or delayed dosing. Sacituzumab govitecan is generally well-tolerated with a manageable safety profile, with side effects no worse than chemotherapy.

References

1. Spring LM, Nakajima E, Hutchinson J, et al. Sacituzumab govitecan for metastatic triple-negative breast cancer: clinical overview and management of potential toxicities. Oncologist. 2021;26:827-834.
2. Dass SA, Tan KL, Selva Rajan R, et al. Triple negative breast cancer: a review of present and future diagnostic modalities. Medicina (Kaunas). 2021;57:62.
3. Wahby S, Fashoyin-Aje L, Osgood CL, et al. FDA approval summary: accelerated approval of sacituzumab govitecan-hziy for third-line treatment of metastatic triple-negative breast cancer. Clin Cancer Res. 2021;27:1850-1854.