Advanced Endometrial Cancer - Episode 14

Novel Targets for Advanced Endometrial Cancer

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Bradley J. Monk, MD, FACS, FACOG: We’ve talked about chemotherapy regimens, and I’d like to finish with a couple of them. Trastuzumab works well with chemotherapy. It really doesn’t shrink tumors alone. There is now this whole concept of adding an oral anti-HER2 TKI [tyrosine kinase inhibitor] with an antibody. That never really worked with the anti-VEGF space, so bevacizumab plus an anti-VEGF TKI. But this idea of tucatinib plus trastuzumab has had some traction in breast cancer. As you can see, we’ve learned a lot from breast cancer biology and we’re leveraging that, such as CDK4/6 in endometrial. Dave, I know you’re working on this, this tucatinib/trastuzumab idea. Tell me, does that make any sense? Are you excited about it? I hope you are, because I am.

David M. O’Malley, MD: I’m so glad you pronounced that. That’s a tongue twister, those 2 in a row, tucatinib and trastuzumab. You’re so good. We just talked about the pan-TKIs and the activity. This is a basket trial. They have to have HER2 overexpression or amplification. Cervix, uterine cancer, biliary tract, urethral and nonsquamous non–small cell lung cancers. Obviously, the uterine cancers are what we’re talking about here. If you have a patient who has overexpression or amplification for HER2/neu, they’ll be put on one of these 5 cohorts. They also have a breast cohort and another GI [gastrointestinal] cohort in these patient selections. They’ll do an initial early first cohort. If they see some activity, that will be expanded into a larger second stage. Hopefully, we’ll see some results as exciting as we’ve seen in breast cancer.

Bradley J. Monk, MD, FACS, FACOG: With your leadership and since HER2 is so commonly over expressed in serous cancers, you’ve allowed prior adjuvant chemotherapy, trastuzumab to be eligible. And again, I know Brian, you’re the chemotherapy-free “ambitionist.” You get chemotherapy, HER2, you get some maintenance HER2, and then you layer on the tucatinib and you get tumor shrinkage. I’m really excited about this.

This is open in the US Oncology Network. I know you have it open at The Ohio State University and other centers. It all starts, back to our initial conversation, with biomarker testing. Biomarker testing creates the opportunity. Brian, there’s another study that I’m aware of, and I’m sorry to list so many studies, but not really. Because studies are what help us gain discovery in patients and improve outcomes. I apologize that it’s taken so much of our audience’s time. But I’m happy to talk about it. Tell us about selinexor and the SIENDO trial.

Brian M. Slomovitz, MD: Selinexor, this is another large, randomized phase 3 trial in women with advanced endometrial cancer. They get their chemotherapy first, and then following chemotherapy—it’s a maintenance trial. The patients are randomized to selinexor versus placebo in the maintenance trial to help keep the disease away longer. It’s another exiting trial that we’re looking forward to.

Bradley J. Monk, MD, FACS, FACOG: Katie, all of you mentor your colleagues. This is another mentor trial in which Katie Moore is mentoring Debra Richardson, MD, FACOG, FACS. I know you’re passionate about this. Do you have any comments on this? This is a molecule that’s approved for liquid tumors. I’m excited to open, and it’s brand new.

Kathleen N. Moore, MD: Yes. This is an interesting agent. It is now on the NCI CRADA [National Cancer Institute Cooperative Research and Development Agreement], and there are a bunch of studies coming out across solid tumors. It’s a nuclear exporter inhibitor. It hits XPO, so it presents exportive oncogenes. It keeps them localized so that they do their oncogenic things. It has a nice history, proof of principle in hematologic tumors and solid preclinical data. Vicky Makker, MD, who has led a lot of the early development for this asset, just published in Gynecologic Oncology, the work in ovarian cancer, looking at homologous recombination proficient tumors. It has some potential for gynecologic malignancies. This is an interesting opportunity to study it again as maintenance in endometrial cancer. Like trastuzumab, it’s not something we’ve been successful with at this point. But we’re starting to get to a place where we can offer women something other than continuous carbo/taxol [carboplatin, paclitaxel]. The mechanism is very different. There doesn’t seem to be a biomarker yet, but it’s very cool.

Bradley J. Monk, MD, FACS, FACOG: It is the first-in-class nuclear pore inhibitor. As you say, it inhibits trafficking of some of these oncogenic drivers.

Transcript Edited for Clarity