Molecular Testing and Frontline Treatment Options in Endometroid Adenocarcinoma

Video

Centering discussion on first-line therapy in endometroid adenocarcinoma, Matthew A. Powell, MD, highlights molecular targets and treatment options in this setting.

Transcript:

Matthew A. Powell, MD: Molecular testing for endometrial cancers really has come of age. Something we’ve been working on for the last 20 years is to really understand how additional tests beyond our pathology report can help us manage patients with endometrial cancer. Mismatch repair testing or testing for the Lynch syndrome genes is something that initially started now 15, 20 years ago as we were looking for Lynch syndrome. Now we’re looking for therapies and therapeutic choices and prognostic information by testing for the mismatch repair genes. Mostly this is done by immunohistochemistry, staining 4 different mismatch repair genes or by next-generation sequencing to evaluate these genes in that manner, as well as looking at microsatellite instability. As far as these tests, and I’ll get to the additional tests beyond mismatch repair testing, when should they be ordered? Typically, we’re often asking them to be ordered even on the D&C [dilation and curettage] or endometrial biopsy, because they may have some clinical implications for screening and for helping us decide when we should do additional imaging. All this is really evolving. For those patients who have a P53 mutation in their cancer, we are more likely to want to do additional imaging as we plan their surgery. So getting some of that testing done on their D&C specimen makes sense to do. If these tests weren’t done, they certainly should be done at progression or recurrence because they will help us decide the appropriate additional therapies we should consider. In our practice, we often will do HER2 testing to allow either enrollment in a clinical trial or the addition of trastuzumab to carboplatin and paclitaxel, for those patients that are eligible. The role of estrogen receptors and progesterone receptors are still being defined. There are certain populations where we can consider de-escalation of therapy, so [that is] less use of radiation for certain patient populations. That includes the polymerase epsilon group that we’re still investigating whether we should be less aggressively treating those patients who have preliminary epsilon mutations.

Looking at first-line therapy options for a patient who has a proficient mismatch repair or microsatellite-stable endometrial cancer, we really think about chemotherapy. That chemotherapy has been in the form of carboplatin [and] paclitaxel. Now there’s some new information out, which was presented recently at the Society for Gynecologic Oncology meeting and published within the New England Journal [of Medicine], about the addition of a checkpoint inhibitor to that regimen—but that’s not yet approved by the FDA nor the NCCN [National Comprehensive Cancer Network]. At the current time we’re still looking at chemotherapy and that would be our standard for most patients, but we can’t forget about hormonal therapy. There’s a long history of, especially in treating our lower-grade cancers, hormonal therapy and whether that’s a progestational agent or an alternating progestational agent. Something like tamoxifen or an aromatase inhibitor, all those have been investigated. The addition of immune checkpoint inhibitors is, like I said, just very recent and I think [it] will likely become a standard for many patients with advanced measurable disease endometrial cancer. The addition of antiandrogenic agents is really exciting. We know from the combination of lenvatinib and pembrolizumab that this is a very active regimen in the second and third line, as well as it’s been investigated in the frontline with the LEAP-001 trial [NCT03884101]. That trial’s not yet reported, but we anxiously await to see if a nonchemo regimen could be used for these patients. There’s also the combination of chemotherapy plus bevacizumab, which does have NCCN compendium listing, that has been an option for certain patients. There’s some translational science that came out of [the] GOG-86P [trial] [NCT00977574] that looks at the patients who have P53G mutation and may be the ones most likely to benefit from the addition of bevacizumab. Although that’s kind of hypothesis-generating data, it has been included within the NCCN to allow us to use the combination of carboplatin, paclitaxel, and bevacizumab. How do we decide between available options for a given patient and how does prior therapy impact selection? Giving chemotherapy adjuvantly. Not necessarily the case that we presented, but a lot of our patients with stage 1 or 2 disease will get treated adjuvantly with carboplatin-paclitaxel, especially those serous cancer patients. When those patients recur, what should we be thinking about? Do we go to a nonchemo regimen or do we continue with chemotherapy again in the form of carboplatin-paclitaxel, maybe adding in bevacizumab? We’ll talk a little more about that. Some of that re-treatment has to do with [adverse] effects the patient incurred with prior therapy and the thoughts on an immunotherapy regimen for this patient. That usually would mean lenvatinib and pembrolizumab is what we would select in the second- and third-line setting at this point.

Transcript edited for clarity.

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