Dostarlimab Plus Carboplatin And Paclitaxel for Patients With Primary Advanced or Recurrent Endometrial Cancer

Results From the Phase 3 RUBY Trial

Matthew Powell, MD, Washington University School of Medicine in St Louis, Missouri, shares results from the phase 3 RUBY trial, evaluating dostarlimab plus carboplatin and paclitaxel, followed by dostarlimab monotherapy among patients with endometrial cancer.

In this trial, the dostarlimab plus carboplatin–paclitaxel demonstrated a statistically significant and clinically meaningful improvement to overall survival, with an acceptable safety profile. These results led the US Food and Drug Association (FDA) to expand the indication for this regimen to all patients with primary advanced or recurrent endometrial cancer.

Dr Powell stated, “This obviously represents a great step forward for our patients with very hard-to-cure malignancies, and we are starting to use that word, ‘cure,’ now for these patients, even though they have advanced stage disease.”

Transcript:

Hi, I'm Dr Matthew Powell, I'm a gynecologic oncologist at Washington University School of Medicine in St. Louis, Missouri, and I was the US lead for the RUBY trial, which just over a week ago, on July 31st, we received work from the FDA that dostarlimab combined with carboplatin and paclitaxel chemotherapy was approved for patients, not only with defective mismatch repair cancers, but really all types of endometrial cancer that is recurrent or advanced. That’s a big step forward for our patients, and this came out of data from the RUBY trial.

The RUBY trial was a large prospective placebo-controlled, randomized trial of patients with advanced or recurrent endometrial cancer. Most of these patients had measurable disease and were stratified based on their mismatch repair status, so whether they were [microsatellite instability] MSI-high or not, and randomized in a 1-to-1 fashion to receive carboplatin-paclitaxel, plus/minus dostarlimab. This trial reported the initial results now 2 years ago, showing dramatic improvement in progression-free survival, especially in the patients with defective mismatch repair, but also a strong trend within the proficient mismatch repair group.

These patients might have had radiation therapy, and we've done a lot of analyses looking at the different cohorts of patients. Who benefits most really looks to be the defective mismatch repair patients, but there are really clinically meaningful benefits for the patients with proficient mismatch repair.

The trial also showed an overall survival benefit, which was presented this March at the SGO Meeting and showed an improvement, again, most dramatic in the mismatch repair deficient population, but also seeing that strong trend in not only the overall population, but in that proficient mismatch repair population.

There were immune-related adverse events, as we'd expect from a PD-1 inhibitor, including pneumonitis, hepatitis, and other endocrinopathy, such as hypothyroidism. These patients basically did about what we expected — there were no new safety signals with the combination of this in chemotherapy.

I'm quite excited to say that this wasn't only just approved in the United States, but also within Canada and some of our European countries as well. This obviously represents a great step forward for our patients with very hard-to-cure malignancies, and we are starting to use that word, “cure,” now for these patients, even though they have advanced stage disease.

Source:

Powell MA, Biorge L, Willmott L, et al. Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin–paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial. Ann Oncol. Published online: June 9, 2024. doi: 10.1016/j.annonc.2024.05.546

FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy.Published online: August 1, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy