Triple-Negative Breast Cancer Treatment

From 1 May 2022, sacituzumab govitecan is available on the Pharmaceutical Benefits Scheme (PBS) for unresectable locally advanced or metastatic triple-negative breast cancer. The PBS listing requires patients to have progressive disease following at least two prior systemic therapies, with at least one of them in the locally advanced or metastatic setting.

Sacituzumab govitecan is an antibody-drug conjugate (ADC). The antibody binds to Trop-2 (trophoblast cell-surface antigen-2) which is highly expressed in many cancers, including breast cancer. A hydrolysable linker joins this antibody to the cytotoxic drug, SN-38. The SN-38 molecule is a topoisomerase I inhibitor and the active metabolite of irinotecan. Following intravenous administration, the ADC binds to Trop-2 on the tumour cell surface which allows for targeted delivery of SN-38. The cytotoxic effect of SN-38 is achieved through DNA damage which leads to apoptosis and cell death.

The ASCENT trial compared sacituzumab govitecan with single-agent chemotherapy (physician’s choice of eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-negative breast cancer. The primary endpoint of median progression-free survival was 5.6 months with sacituzumab govitecan and 1.7 months with chemotherapy. The median overall survival was also greater (12.1 months versus 6.7 months), as was the objective response rate (35% versus 5%). The most common adverse events in the sacituzumab govitecan group were neutropenia (63%), diarrhoea (59%), and nausea (57%). Treatment discontinuation due to adverse events occurred in 5% of patients in each group.

Pre-medication is recommended prior to each dose to prevent infusion reactions and chemotherapy-induced nausea and vomiting.