Sacituzumab govitecan in breast cancer

Abstract

: Sacituzumab Govitecan (SG, IMMU-132) is an antibody-drug conjugate that links the irinotecan active metabolite, SN-38 to a humanized monoclonal antibody targeting Trop-2, a transmembrane calcium signal transducer. Trop-2 is highly expressed in epithelial cancer cells of multiple tumor types, including breast cancer. Therefore, the anti–Trop-2 monoclonal antibody allows for targeted delivery of SN-38 to tumor cells. SN-38 is membrane permeable and may elicit antitumor effects in adjacent tumor cells (bystander effect) before internalization of the antibody–drug conjugate through hydrolysis of the linker or by intracellular SN-38 release after internalization. SG has been approved to treat patients with triple-negative breast cancer (TNBC) and patients with urothelial cancer in US. In phase III confirmatory ASCENT trials, SG showed more significant efficacy benefit in TNBC patients who had received at least two prior systemic therapies than treatment of physician choice. Neutropenia and diarrhea are the most common adverse events and can be managed with supportive care. The incidence of treatment discontinuation due to adverse events was low (<5%). Evidence has shown that SG should be considered as a new standard of care in patients with pretreated metastatic triple-negative breast cancer (mTNBC). Besides, SG has shown encouraging activity in patients with pretreated HR+/HER2− mBC with a predictable, manageable safety profile. Here, in this review article, we summarize recent studies of SG for breast cancer treatment and provide a systematic review of the recently developed therapeutic approach.