Dr Aditya Bardia on How Combining Sacituzumab Govitecan, Talazoparib Amplifies Treatment Response

October 12, 2020

There is a synthetic lethality between sacituzumab govitecan and a PARP inhibitor, noted Aditya Bardia, MBBS, MPH, breast medical oncologist, Massachusetts General Hospital, Harvard Medical School.

There's a lot of biological and preclinical rationale for the combination of sacituzumab govitecan, a topoisomerase inhibitor, and talazoparib, a PARP inhibitor; there is a synthetic lethality, or synergy, between them, noted Aditya Bardia, MBBS, MPH, breast medical oncologist, Massachusetts General Hospital, Harvard Medical School.

Transcript

How are the individual benefits of sacituzumab govitecan and talazoparib amplified in a combination treatment?

So, at virtual ESMO [European Society of Medical Oncology annual meeting], we presented the results of the ASCENT trial, which showed that patients who receive sacituzumab govitecan have a superior progression-free survival as compared to standard chemotherapy. The median progression-free survival was 5.6 months versus 1.7 months with standard chemotherapy. And even in terms of overall survival, patients who receive sacituzumab govitecan had an overall survival of 12.1 months as compared to 6.7 months with standard chemotherapy, with the hazard ratio of 0.48.

So, these results confirm that sacituzumab govitecan should be the new standard of care for patients with metastatic triple-negative breast cancer. The question is: moving forward, what should be done? And there's a lot of interest in combining this agent with other targeted therapies, including PARP inhibitors.

At ESMO, we also presented our trials in progress, a poster looking at the combination of sacituzumab govitecan with the PARP inhibitor, talazoparib. And there's a lot of biological and preclinical rationale for this combination. SN-38 is a topoisomerase inhibitor [that] induces single-strand DNA breaks, and in terms of repair of the DNA is reliant on the DNA repair pathways, including the PARP pathway. So, if you use a PARP inhibitor, it prevents the repair of the DNA and also prevents the cancer cells from repairing the DNA and replicating.

So, there's this synthetic lethality, or synergy, between SN-38, or sacituzumab govitecan, [and] a PARP inhibitor, so we're doing a phase 1B clinical trial combining these 2 agents, sacituzumab govitecan with a PARP inhibitor, talazoparib.