govitecan

Sacituzumab govitecan, sold under the brand name Trodelvy, is an antibody-drug conjugate approved for certain metastatic cancers. It consists of a humanized antibody targeting Trop-2 linked to SN-38, the active metabolite of irinotecan, via a hydrolyzable linker. Trop-2 is a cell-surface antigen overexpressed in many epithelial cancers, making it a target for delivering cytotoxic therapy.

The mechanism involves binding to Trop-2–expressing tumor cells, internalization, and release of SN-38 in the tumor microenvironment, where it inhibits topoisomerase I and causes DNA damage. The linker also enables a bystander effect, potentially killing neighboring cancer cells with low antigen expression and increasing antitumor activity.

Sacituzumab govitecan was developed by Immunomedics and later acquired by Gilead Sciences in 2020. It received FDA approval in 2020 for adults with metastatic triple-negative breast cancer who had at least two prior therapies, and in 2021 for adults with metastatic urothelial cancer after platinum-containing chemotherapy. It has been studied in additional tumor types and settings.

The drug is administered by intravenous infusion in cycles, typically every 21 days, with dosing based on body weight and adjusted for toxicity. Common adverse events include neutropenia, fatigue, diarrhea, and nausea; more serious risks include febrile neutropenia and dehydration. As with all cytotoxic therapies, it requires monitoring of blood counts and organ function and may be contraindicated in certain medical conditions.

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