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.
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