Personalized Treatment Pathways in Endometrial Cancer: A Molecular Approach

ReachMD Announcer:
You’re listening to Project Oncology on ReachMD. On this episode, we’ll hear from Dr. Kathleen Moore, who’s a gynecologic oncologist and the Director of the Oklahoma TSET Phase I Program at OU Health Stephenson Cancer Center in Oklahoma City. She’ll be discussing the future of molecular profiling and targeted therapies in endometrial cancer. Here’s Dr. Moore now.

Dr. Moore:
There's been further drilldown into these different molecular subgroups really trying to individualize therapies to the right molecular groups. So, for example, the group of tumors that are TB53 mutated are largely not deficient mismatch repair. They're almost mutually exclusive, not entirely. But that group of tumors are largely serous. They have a relatively high incidence of HER2 expression1+, 2+, 3+. They have more folate receptor alpha expression, and so bringing in antibody drug conjugates in this setting bringing in even just trastuzumab aloneis under study. There's different small molecules WEE1 kinase, CHK1/2 inhibitors. ATR inhibitors are of interest in this group because they have a very specific molecular profile, so we may treat them differently in the future, and studies are ongoing there.

And then in the group of tumors that are what we say copy number low and not mismatch repair deficient, we now call them NSMP, no specific molecular profile. This is where tumors that are driven by or may be driven by hormone receptors live, and so there's a real interest in looking at those tumors differently as well. And so I think what you're seeing now is an expectation that, at least in the metastatic recurrent setting, patients are going to get chemotherapy with immune checkpoint inhibitors if they’re deficient mismatch repair. They could get immune checkpoint inhibitor if they're proficient.

But then you're going to start seeing the sequencing of things here, at least in the second line and third line, with antibody-drug conjugates looking quite active in this space, where the benchmark of efficacy is monotherapy chemo. 15 percent response rates. It’s abysmal. And now we're seeing early reports of these antibody-drug conjugates coming in with response rates in the 30, 40, 50 percent.

You're seeing the emergence of these small molecules, and you're also seeing a renewed interest in endocrine therapies, specifically for this NSMP subgroup. The other thing you're going to see is an attempt to bring more biomarker-directed therapies into adjuvant settings in tumors with a high risk of recurrence.

So there's just a lot going on right now that in the end. Once it's all filtered out, I believe we'll really establish a much more individualized biomarker and/or molecular profile-based therapeutic decision making for patients from the beginning that, my expectation is, will at the very least improve overall survival in general but may actually also lead to more patients who are cured and don't have to have sequential lines of therapy. That's the goal. There's a lot of work to do, but a lot of excitement too.

ReachMD Announcer:
That was Dr. Kathleen Moore talking about emerging treatment options in endometrial cancer treatment. 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!