Addressing the Mechanism of Action for the AKT Pathway in TNBC
May 26, 2020 10:00pm
By Rebecca Dent, MD
Aditya Bardia, MD, MPH, discusses the efficacy of sacituzumab govitecan in patients with triple-negative breast cancer.
Aditya Bardia, MD, MPH, a medical oncologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, discusses the efficacy of sacituzumab govitecan (Trodelvy) in patients with triple-negative breast cancer (TNBC).
Of the many antibody drug conjugates in clinical development at the moment, Bardia says the furthest along for metastatic TNBC is sacituzumab govitecan. This antibody drug conjugate targets TROP-2, which is overexpressed in most TNBC cells. It is also links to SN-38, the active metabolite of irinotecan (Onivyde) and is a topoisomerase inhibitor.
In a phase I/II clinical trial investigating sacituzumab govitecan in a heavily pretreated patient population (NCT01631552), there was impressive clinical activity with a response rate of over 30%, according to Bardia. In this setting, there is usually a response rate of about 10% to 15% with standard chemotherapy. The responses for this therapy were durable as well.
The toxicity profile for an antibody drug conjugate is usually caused by the toxic payload, and depending on the type of toxic payload, patients will have different adverse events (AEs). Because sacituzumab govitecan has an SN-38 toxic payload, common AEs include myelosuppression, such as neutropenia and thrombocytopenia; gastrointestinal AEs, such as nausea and diarrhea; and alopecia.