Promising Novel Targets for Endometrial Cancer Management

EP: 1.Endometrial Cancer Incidence and Risk Classification

EP: 2.Genomic Assessments for Metastatic Disease

EP: 3.Treatment Challenges: Advanced Endometrial Cancer

EP: 4.Adjuvant Chemotherapy +/- Radiotherapy: Recent Data

EP: 5.Second-Line Checkpoint Inhibitor for MSI-H Disease

EP: 6.GARNET Clinical Trial Regimen in Advanced Disease

EP: 7.Rationale for Combination Therapy in Advanced EC

EP: 8.Safety/Efficacy Results From EC Cohort of KEYNOTE-146

EP: 9.Impact of Pembrolizumab/Lenvatinib Approval in EC

EP: 10.Therapy Sequencing Through Multiple Lines of Therapy in EC

EP: 11.Novel Strategies in Development for EC Management

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EP: 12.Promising Novel Targets for Endometrial Cancer Management

EP: 13.Case 2 Discussion and Considerations for Second-Line Treatment Selection

David M. O’Malley, MD: What other agents are we looking at? Some of them I already mentioned. We’re looking at PARP inhibitors and tumors, which behave like ovarian cancers, like serous cancers. Can we predict the response in those?

There are the PI3-kinase mutations, so we have these inhibitors. The problem with that has obviously been the hyperglycemia, but we’re getting better at figuring that out. When we look at these agents, some of the other options are taking the hormonal therapy as they have in breast cancer and trying to combine it with some of these newer agents. We have an agent approved in breast cancer, the CDK4/6 inhibitors. We’re now looking at it in uterine cancer, combining that with hormonal therapy and trying to see improved results in patients who seem to have hormonally receptive tumors.

We’ve talked about the HER2 [human epidermal growth factor receptor 2]/neu candidates, those antibody-drug conjugates also being developed in breast cancer. Why wouldn’t they work in uterine cancer? We’re studying those. Dr Joyce Liu presented a WEE1 inhibitor, looking at it in serous cancers of the uterus, with very interesting results. As we look at these, it comes back to what I said: Check the next-generation sequencing, look for a targetable mutation, and find a clinical trial. Even outside clinical trials, there are some options for these patents.

As we look at endometrial cancer, we need to understand what’s going on regionally. I still believe there is a role to check lymph nodes. Sentinel lymph nodes is now a minimally invasive surgery. Why not get that information? I really want us to see if radiation is adding much of anything. We really need to answer this question. I say that, but if I have a patient with local-regional disease and know that radiation has been shown to be beneficial, I have a hard time omitting it.

I’m old-school. I admit it. My friend Dr Brian Slomovitz is going to beat me up for saying that. But that’s a really important question. Most important is this: I used to look at these patients after they completed carboplatin-paclitaxel and say, “Sorry, there’s not much else for you. We can try some hormones.” Now these patients are living years. Just in my practice yesterday, I had 2 patients who have a recurrence for 4 years. It’s almost unheard of prior to this new era that we live in. We are in the most exciting time of drug development ever. Let’s continue to get our patients these options. The best way to do that is through clinical trials.

Transcript Edited for Clarity