Advancing Endometrial Cancer Care: ADCs and Biomarker-Based Therapies

ReachMD Announcer:
You’re listening to Project Oncology on ReachMD. On this episode, we’ll hear from Dr. Brian Slomovitz, who’s the Director of Gynecologic Oncology and Co-Chair of the Cancer Research Committee at Mount Sinai Medical Center as well as a Professor of Obstetrics and Gynecology at Florida International University in Miami. He’ll be discussing current and emerging advances in endometrial cancer treatment. Here’s Dr. Slomovitz now.

Dr. Slomovitz:
I think the next exciting step in the management of endometrial cancer will be the further development of antibody drug conjugates, or ADCs. There's three components: an antibody that is attracted to tumor cells, a kill the chemotherapy agent or the payload and then the linker. The linker's job is to bring the chemo to the cell and then let go of it when it's at the cancer cell.

These are under development. Actually, there's one ADC, trastuzumab deruxtecan, which targets HER2, a protein located on endometrial cancers. It's been looked in later-line therapies in something called the PanTumor DESTINY trial, and it actually led to an FDA approval already in patients with advanced disease with 3+ expression of HER2.There's also a Compendium or NCCN listing of 2+ OR 3+. But the number of ADCs that we're evaluating goes way beyond that. We're evaluating ADCs targeting TROP2, targeting B7H4, targeting alpha folate receptor in addition to further studies looking at trastuzumab deruxtecan.

One of the exciting areas that we have in the treatment of endometrial cancer is biomarker-driven therapies. We know about it with deficient mismatch repair. That's a biomarker-driven strategy. We know about it with estrogen receptor positivity. There are potentials for biomarker-driven strategies here. P53 is a tumor suppressor gene located in cells, and we find that that's also another target. It's interesting. When we think of targets, we think of things that are mutated. Actually, it's the wild type P53 that's a potential target for one of the advances we have in endometrial cancer.

Selinexor is a nuclear transport inhibitor. It keeps good proteins in the cell. We did a study looking at selinexor, the nuclear transport inhibitor, in patients with advanced recurrent disease in the maintenance setting after responding to chemotherapy. This was called the SIENDO trial. The SIENDO trial was negative. However, in the subgroup of patients that had P53 wild type tumors, it was extremely positive. It showed that it worked. So being that it was a negative study, that was a primary objective.

The next step that we did is that we are looking at a study that we call the EXPORT trial, specifically in patients with P53 wild type tumors as the biomarker selinexor maintenance versus placebo maintenance to see if that could be incorporated into the standard of care for our patients. It's still experimental now, but based on the earlier prespecified data, there's some excitement into that combination. Now what that will do if it's positive, it may push immunotherapy later line into the therapy, but we'll see.

ReachMD Announcer:
That was Dr. Brian Slomovitz talking about what’s new in endometrial cancer management. To access this and other episodes in our series, visit Project Oncology on ReachMD.com, where you can Be Part of the Knowledge. Thanks for listening!