Closing out her discussion on the management of recurrent metastatic endometrial cancer, Bhavana Pothuri, MD, highlights ongoing clinical trials and novel treatment modalities.
Bhavana Pothuri, MD: The real unmet need in endometrial cancer is the high-risk histologic subtypes. A recent study noted that endometrial cancer mortality is increasing. It’s nearing that of ovarian cancer, and it’s soon to surpass the mortality of ovarian cancer. Clearly, we need to do better with this disease. The reason for this is 2-fold: 1, we’re seeing the increasing obesity epidemic, and 2, we’re seeing a higher proportion of high-risk histologic subtypes. Those are mostly in racially and ethnically diverse patients. Black patients have a very high preponderance of uterine serous cancers, which have a much poorer prognosis. We have treatments for front line and second line that are effective. After chemotherapy in the front line, we have lenvatinib and pembrolizumab for the MMR [mismatch repair]–proficient patients. For dMMR [MMR deficient], we have both dostarlimab and pembrolizumab. These treatments have very good efficacy, so the critical unmet needs at this point are therapies beyond this.
The idea is to identify effective therapies in the later-line setting and move them into the front line, so we can try to effect more cure. Once the disease has relapsed, we rarely can cure patients. The strategy is to move these agents into the frontline setting. LEAP-001 is looking at the combination of pembrolizumab and lenvatinib in the first-line setting to replace chemotherapy. The RUBY trial is evaluating paclitaxel-carboplatin with dostarlimab vs paclitaxel and carboplatin alone. We’ll have to await the results, which should be coming at any time. I would love to see these move into the frontline setting.
What are we going to do after? What other promising treatments am I excited about? There are CDK4/6 inhibitors with hormonal agents that are exciting for our hormonally driven or copy number low tumors. We’ve also heard about selinexor, which inhibits XPO1, and it has been shown to have efficacy in TP53 wild-type patients. In addition to that, there are some exciting antibody-drug conjugates on the horizon. There are agents such as STRO-002, mirvetuximab, and MORAb-202. There are also HER2 [human epidermal growth factor receptor 2]–directed therapies that are very exciting and small-molecule inhibitors, such as tucatinib. HER2 antibody-drug conjugates recently have had exciting data and approvals in breast cancer. Finally, the WEE1 inhibitors are an exciting target in uterine serous cancers. As I stated earlier, the uterine serous cancers are noted in Black patients and are a true unmet need. I’m hoping we have some of these therapies available to use in our patients going forward.
I’m most excited about awaiting the data from RUBY, LEAP-001, and GY018, but that’s going to come a little later because that’s still enrolling. These are trials that may be practice changing and may change the way we approach the frontline treatment of endometrial cancer, so I’m looking forward to those data.
Transcript edited for clarity.