Endometrial Carcinoma Treatment Advances - Episode 5

Novel Strategies Being Investigated in Endometrial Cancer

Brian Slomovitz, MD, MS, FACOG, shares excitement for novel and combination therapies being investigated in the endometrial cancer landscape.


Brian M. Slomovitz, MD, MS, FACOG: The landscape for endometrial cancer is very exciting. We have 5 first-line global trials evaluating immunotherapy pushed into the first line. Four of these trials are looking at chemotherapy plus or minus immunotherapy, and the fifth is looking at lenvatinib-pembrolizumab vs chemotherapy carboplatin-paclitaxel in the first-line setting. There’s no doubt that if any trials are positive, the treatment paradigm will change and will move I/O [immuno-oncology] to the first-line setting.

There are also great areas of research being done in the second line to determine better treatment options for those patients, which represents a complete unmet need. The first thing we’re looking at is immunotherapy after immunotherapy. Meaning that in patients who fail immunotherapy, is there a role for additional immunotherapy? Another area has been biomarker-driven research. PTEN or PI3-kinase pathway mutations are very common in endometrial cancer.

Looking at the biomarker inhibitors that work in this disease, we found that mTOR inhibitors have good efficacy compared with traditional hormonal therapies. A study I did, GOG-3007, compared everolimus and letrozole vs Megace and tamoxifen. In this study, although we had comparable response rates, the progression-free survival with the combination of everolimus and letrozole, an mTOR and an aromatase inhibitor, was improved compared with Megace and tamoxifen. In addition, in the subset analysis, we looked at patients who are naïve to chemotherapy. In those patients, we had similar response rates to chemotherapy alone and longer progression-free survival in a cross-trial comparison, 21 months vs 14 months. At 1 recent meeting, there were data presented for a newer mTOR inhibitor with hormonal therapy, and it continued to demonstrate the benefit of this combination.

In addition, CDK4/6 inhibitors are being investigated in combination with hormonal therapy for the treatment of this disease. My close colleague in Denmark, Dr Mansoor [Raza] Mirza, presented a paleo study looking at the combination of CDK4/6 inhibitor plus letrozole vs letrozole alone. In this trial, he found a significant improvement in progression-free survival in the CDK4/6 plus letrozole vs letrozole. Finally, in another subset, uterine serous cancers, we’re looking at WI-1 inhibitors. Based on some great work at Dana-Farber [Cancer Institute], they demonstrated activity in this subset of endometrial cancers. There are more ongoing trials being done to evaluate this pathway in pretreatment of uterine serous cancers.

Transcript edited for clarity.