ENGOT, NSGO-CTU & GOG-Foundation proudly announce the ground-breaking results of the ENGOT-EN6-NSGO/GOG-3031/RUBY trial.

The results reveal improvement in overall survival at 24 months in the whole study population from 56% (CP+placebo) to 71.3% (CP+dostarlimab). “although these are interim data, we believe they are robust and will be confirmed with longer follow-up.”, said Mansoor R Mirza.

The trial is presented on the 27th of March 2023 through ESMO’s Virtual Plenary and at the Society of Gynecologic Oncology’s (SGO) Annual Meeting on Women’s Cancer. The trial’s results are simultaneously published in the New England Journal of Medicine, demonstrate unprecedented improvement in Progression-Free Survival and Overall Survival of patients with primary advanced or recurrent endometrial cancer (EC) when treated with dostarlimab in combination with standard-of-care carboplatin/paclitaxel (CP) followed by dostarlimab monotherapy compared to chemotherapy alone.

“Carboplatin/paclitaxel is the standard of care for first-line treatment of primary advanced or recurrent endometrial cancer; however long-term outcomes remain poor, with median overall survival of less than 3 years. Anti–PD-1 based therapy has transformed the management of endometrial cancer post-platinum chemotherapy, however, advances in first-line systemic treatment were urgently needed”, says study chair Mansoor Raza Mirza (NSGO-CTU). “These results are unprecedented and shall considerably improve the outcome of our patients”.

Statement by ENGOT President Prof. Nicoletta Colombo:

“The results of this ENGOT-GOG-F trial represent an incredible step forward in our battle against advanced endometrial cancer. Our patients can now benefit from a new first line standard of care able to significantly prolong progression-free survival and potentially overall survival. Another success of the strong collaboration among gynecologic oncology groups worldwide. “

Statement by GOG-F President, Larry J. Copeland, MD:

“This trial’s practice-changing results help all patients who are undergoing treatment for advanced endometrial cancer. ENGOT and the GOG Foundation’s goals are to improve the lives of patients through clinical trials. This important research allows the discovery of new and effective therapies to transform the standard of care in gynaecologic oncology. Our collaborative efforts continue to bring treatments to our patients sooner.”

About RUBY Trial

The RUBY trial is a phase 3, randomised, double-blind, multicenter, placebo-controlled study. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomised 1:1 to receive dostarlimab, or placebo, plus carboplatin/paclitaxel (CP) combination, followed by dostarlimab or placebo monotherapy.  

Of 494 patients randomised, 118 (23.9%) had dMMR/MSI-H tumours. Progression-free survival (PFS) was significantly longer in the dostarlimab plus CP arm than the placebo plus CP arm in patients with dMMR/MSI-H tumours and in the overall population. In the dMMR/MSI-H population, the estimated Kaplan-Meier (KM) probability of PFS at 24 months was 61.4% (95% CI, 46.3–73.4) with dostarlimab–CP and 15.7% (95% CI, 7.2–27.0) with placebo–CP (HR, 0.28; 95% CI, 0.162–0.495; P<0.0001).

In the overall population, the estimated KM probability of PFS at 24 months was 36.1% (95% CI, 29.3–42.9) with dostarlimab–CP and 18.1% (13.0–23.9) with placebo–CP(HR, 0.64; 95% CI, 0.507–0.800; P<0.0001). The estimated KM probability of overall survival (OS) at 24 months was 71.3% (95% CI, 64.5–77.1) with dostarlimab plus CP and 56.0% (95% CI, 48.9–62.5) placebo plus CP (HR, 0.64; 95% CI, 0.464–0.870). The safety profile of the combination was generally consistent with the safety profiles of the individual components. The most common treatment-emergent adverse events reported for dostarlimab–CP compared with placebo–CP arms were nausea (53.9% and 45.9%), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%).

In conclusion, Dostarlimab + CP demonstrated statistically significant and clinically meaningful PFS benefit with an early OS trend:

• Substantial, unprecedented benefit in dMMR/MSI-H patients
• Clinically meaningful long-term benefit observed in MMRp/MSS patients

Dostarlimab plus carboplatin/paclitaxel represents a new standard of care for patients with primary advanced or recurrent endometrial cancer.

Source: The GOG Foundation Inc