There is a clear need for better therapies to treat triple-negative breast cancer, especially when progression-free survival is around 2%, says Aditya Bardia, MBBS, MPH, breast medical oncologist at Massachusetts General Hospital, Harvard Medical School.
There is a clear need for better therapies to treat triple-negative breast cancer, says Aditya Bardia, MBBS, MPH, breast medical oncologist at Massachusetts General Hospital, Harvard Medical School, when discussing the results of the phase 3 ASCENT trial that he presented at this year’s virtual European Society for Medical Oncology (ESMO) conference.
What study and data did you present at ESMO?
On behalf of the coauthors, I presented the results of the ASCENT trial, a randomized phase 3 study of sacituzumab govitecan vs treatment of physician’s choice for patients with previously treated metastatic triple-negative breast cancer.
As a background, triple-negative breast cancer represents the aggressive form of breast cancer. It tends to affect young women, African Americans, and clinically is an unmet need. The response rate to standard chemotherapy is in the range of 5% to 10% and median progression-free survival around 2 months. So there’s a need for better therapies.
We’ve been involved with the development of an agent called sacituzumab govitecan, which is a novel antibody-drug conjugate. It targets TROP2, which is overexpressed in a majority of triple-negative breast cancers. The antibody against TROP2, it has a hydrolyzable linker, and the payload linked to the antibody is SN-38, the active metabolite of irinotecan.
So this antibody-drug conjugate has 3 unique properties. The first is that it’s highly specific for TROP2; it’s a first-in-class TROP2 antibody-drug conjugate. Second, it has a high drug to antibody ratio; on average, 7.6 SN-38 molecules per antibody. And third, hydrolysis of the linker allows SN-38 release extracellularly, resulting in bystander effect. Thus, it can affect cells that have low expression of TROP2 or even no expression of TROP2 because of this bystander [effect].
[In] the phase 1/phase 2 trial, a response rate of 33% was seen with this agent, which resulted in accelerated approval earlier this year by the FDA. So, the ASCENT trial was the confirmatory phase 3 trial with this agent comparing sacituzumab govitecan vs treatment of physician’s choice, and the primary end point of the study was progression-free survival.