At the 2023 Society of Gynecological Oncology’s Annual Meeting on Women’s Cancer in Tampa, FL, Mansoor Raza Mirza, MD, Copenhagen University Hospital, Denmark, presents the results of the RUBY trial, investigating the efficacy and safety of dostarlimab plus chemotherapy in the first-line setting for patients with primary advanced or recurring endometrial cancer.

With the improvement in progression-free survival and overall survival for patients treated with dostarlimab plus chemotherapy vs placebo plus chemotherapy seen in this trial, Dr Mirza stated, “we have changed the landscape of treatment of our patients.” He went on, “Dostarlimab plus carboplatin and paclitaxel is a new standard of care for all patients and for dMMR patients with recurrent disease or advanced disease.”

Transcript

Hi, my name is Mansoor Raza Mirza. I'm clinical oncologist from Copenhagen University Hospital in Denmark, and I'm also Medical Director of Nordic Society of Gynecological Oncology.

It has been a great privilege to present the data of RUBY trial, which is ENGOT-EN-6-NSGO/GOG3031 trial. This trial is changing the landscape of treatment of endometrial cancer, and we will, in summary, will save lives of our patients. It has incredible, unprecedented positive results.

The trial is on dostarlimab, which is a PD-1-inhibitor. We have added dostarlimab to standard-of-care chemotherapy that you give in the first line in locally advanced or in the first line at the first recurrence, which is carboplatin and paclitaxel. The rationale is that we believe, and biologically it makes sense, that chemotherapy can increase the sensitivity of the cancer cells, make them immunogenic. We believe that we could combine the treatment with chemotherapy and that will also have efficacious effect, not only on the DNA mismatch repair (MMR) deficient tumors, which is about 25 to 30% of population in endometrial cancer, but also in the MMR proficient tumors.

The trial had randomized all patients with stage 3 and 4 or first relapse. The beauty of this trial is that we have taken all the epithelial histologies, like carcinosarcomas, which is quite a tough disease. The second thing is that patients who had received adjuvant therapy for early-stage disease and have progressed, the treatment-free interval we had allowed was 6 months or more. This makes this trial quite unique. Another unique thing is that this trial has a primary end point of overall survival (OS), not only progression-free survival (PFS).

We randomized patients 1-to-1 to receive 6 cycles of chemotherapy with carboplatin/paclitaxel every 3 weeks and added dostarlimab or placebo every 3 weeks. After chemotherapy, patients continued with monotherapy with dostarlimab or placebo every 6 weeks up to 3 years. As I said, the primary end points were PFS and OS. Patients were stratified according to the MMR deficient (dMMR) status and others.

When we look at the results, they are outstanding. We have 3 primary end points, and we have a follow-up of 25 months. In the dMMR population, we have a PFS benefit at 24 months from 15% for the placebo arm to 61% in the dostarlimab arm, which is unprecedented. The same is the case for the overall population where at 24 months, PFS has increased from 18% to 36%. Even more important is the overall survival data in overall population. Although we have only 33% maturity, where we can already see that Kaplan-Meier curves are separating nicely and there is 25% improvement in overall survival, which is again unprecedented.

When we look at the toxicity profile, there are no new signals. It's the same toxicity you see with single agents, so there is nothing special there. If you look at the patient-reported outcomes, it seems like that the patients are reporting better quality of life in the dostarlimab arm than in the placebo arm.

In conclusion, I would say that we have changed the landscape of treatment of our patients. Dostarlimab plus carboplatin and paclitaxel is a new standard of care for all patients and for dMMR patients with recurrent disease or advanced disease. If you need more information, the paper will be out in New England Journal. Thank you.

Source:

Mirza M. “Dostarlimab in combination with chemotherapy for the treatment of primary advanced or recurrent endometrial cancer: a placebo-controlled randomized phase 3 trial (ENGOT-EN6-NSGO/GOG-3031/RUBY)” Presented at SGO Annual Meeting on Women's Cancer; March 25-28, 2023; Tampa, FL