Emerging Combination Treatments for Patients With Endometrial Cancer


Dr Matthew A. Powell shares some closing thoughts on emerging agents and combination therapies in the endometrial cancer treatment landscape.

Matthew A. Powell, MD: When we think about what’s next in endometrial cancer, there’s a lot going on. The antibody-drug conjugates directed against HER2 seem to have some exciting results. As we saw recently from Dr [Kathleen N.] Moore, the DB-1303 compound is an anti-HER2 IgG1 monoclonal antibody. This study is still ongoing, but the patients in the trial included patients [with] endometrial cancer. At least preliminarily, there were some good responses in the endometrial and ovarian cancer population.

Additional combinations out there [were as follows]. Dr [Alessandro] Santin, [MD], presented the update of the TROP1-directed antibody-drug conjugate. And we saw quite impressive response rates in that population. [It was] a good, tolerable drug with the use of the TROP2-directed antibody-drug conjugate. Many others out there are being developed [in addition to] combinations with checkpoint inhibition. [There’s] the DOMENICA trial, which looks at dostarlimab. This was also presented at ASCO [American Society of Clinical Oncology], and this is chemotherapy alone vs dostarlimab in the frontline advanced setting. [There is] more to come in this [because] it is not yet fully mature. We will see more data about [the following]: Do we need chemotherapy for our patients with defective mismatch repair endometrial cancer? [We have the] same feelings for the KEYNOTE-C93 study, [which is] looking at pembrolizumab for some of these earlier-stage patients. Do they need chemotherapy plus checkpoint, or [is] checkpoint alone enough?

In the future, [for] endometrial cancer management, it’s become clear that we need to know what we’re [managing] molecularly. Profiling is critical. We need to understand which of the TCGA [The Cancer Genome Atlas] subgroups this patient falls into. Estrogen receptor status is needed, especially for [the] not otherwise specified group or the copy number–low group. ER seems to be a good predictor of which patients will do well, and for those who [have] ER-negative [disease], we need to come up with new strategies for [areas where] they’re having more trouble. [We’re] trying to keep these patients from [having] advanced-stage [disease]. When do we give adjuvant therapy? We do have a trial that has completed accrual, with [NRG]-GY020, through the NCI [National Cancer Institute] that’s giving single-agent checkpoint in the form of pembrolizumab for patients with early-stage, high- [and] intermediate-risk endometrial cancer. That trial has accrued all its patients. We’re waiting to see how much a year’s worth of checkpoint inhibition gives a gain for these patients. [There are] a lot of exciting things in the management of endometrial cancer. New staging has been proposed by FIGO [International Federation of Gynecology and Obstetrics]. It’s receiving a bit of controversy. So [there is] more to come in that area.

Transcript is AI generated for clarity and readability.

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