Two Studies That Will Change the Standard of Care in Endometrial Cancer

— Krishnansu Tewari, MD, calls the two “phenomenal” studies “practice-changing work”

by Greg LaubDirector, Video, MedPage Today April 19, 2023

Immunotherapy combined with standard chemotherapy significantly improved progression-free survival in patients with advanced or recurrent endometrial cancer, according to results from two randomized phase III trials presented at the Society of Gynecologic Oncology annual meeting.

In this exclusive MedPage Today video, Krishnansu Tewari, MDa gynecologic oncologist at the University of California Irvine, offers his initial thoughts about the results and clinical implications of the NRG-GY018 and RUBY trials.

Following is a transcript of his remarks:

There were two phenomenal studies that were just presented. The first one, NRG-GY018, looked at adding pembrolizumab to chemotherapy for newly diagnosed advanced endometrial cancer and recurrent endometrial cancer.

The primary endpoint was progression-free survival, and the median progression-free survival in the experimental arm has not been reached, but the hazard ratio of progression or death was significantly reduced. And this is going to be a practice changing study in the mismatched repair deficient population.

The study was interesting because it had two nested cohorts, so they’re also able to answer the question in the mismatched repair proficient group. And here, the median progression-free survival was doubled even in this more high risk group to treat. So that’s very exciting. And I think the numbers were about 6 to 7 months for the patients on the placebo plus chemotherapy, and about 12, maybe 13 months in the patients who were getting chemotherapy plus pembrolizumab.

So that was very exciting, but equally exciting was the second trial that was presented also in the endometrial cancer population. Also looking at adding checkpoint inhibition to chemotherapy this time with dostarlimab, which is another anti-PD1 agent like pembrolizumab.

The difference with the RUBY study is this RUBY had dual primary endpoints, not just progression-free survival, but also overall survival. They showed a significant improvement in progression-free survival in the mismatched repair deficient population. And although overall survival is not yet mature — I think they have the overall survival of events for a third of the patients — the trends look really good.

In addition, even though they were not able to specifically hone in on the results for the mismatch repair proficient population, the results look very favorable for those patients as well.

So in summary, we have two large phase III randomized trials. RUBY is a little bit of a smaller study than NRG-GY018. But they both met their primary endpoints, significantly improving progression-free survival by adding checkpoint inhibitors to chemotherapy in newly diagnosed advanced stage III, stage IV, and recurrent endometrial cancer. Practice changing work. I’m very excited about it.