VP2-2023: Dostarlimab+chemotherapy for the treatment of primary advanced or recurrent (A/R) endometrial cancer (EC): A placebo (PBO)-controlled randomised phase III trial (ENGOT-EN6-NSGO/GOG-3031/RUBY)

Carboplatin-paclitaxel (CP) is standard of care (SOC) for first-line treatment of primary A/R EC; median OS is <3 yrs. Use of anti–PD-1s with chemo has improved outcomes in multiple tumour types. RUBY (NCT03981796) evaluated the efficacy and safety of the anti–PD-1 dostarlimab (D)+CP in A/R EC compared with CP alone. RUBY is a phase III, global, randomised, double-blind, multicentre, PBO-controlled study. Pts with primary advanced stage III or IV or first recurrent EC were randomised 1:1 to receive dostarlimab 500 mg, or PBO, plus carboplatin AUC 5 and paclitaxel 175 mg/m2Q3W (6 cycles), followed by dostarlimab 1000 mg, or PBO, monotherapy Q6W for up to 3 yrs. Primary endpoints were PFS by investigator assessment per RECIST v1.1 and OS. Graphical method was used for hypothesis testing of PFS in the dMMR/MSI-H population, then the overall population, and OS in the overall population. A prespecified exploratory analysis of PFS in MMR proficient (MMRp)/MS stable (MSS) pts was also performed. Safety was assessed. Of 494 pts randomised (245 D+CP; 249 PBO+CP), 23.9% had dMMR/MSI-H tumours (53 D+CP; 65 PBO+CP), 47.8% had recurrent disease; 18.6% and 33.6% had primary stage III and IV disease, respectively. PFS and OS results are presented in the table. Discontinuation of dostarlimab or PBO due to a TEAE occurred in 17.4% pts receiving D+CP and 9.3% pts receiving PBO+CP. The safety profile of D+CP was generally consistent with the safety profile of each drug.TableVP2-2023HR (95% CI) P% Probability at 24 mo (95% CI)PFSdMMR/MSI-H D+CP0.28 (0.162–0.495)<0.000161.4 (46.3–73.4) PBO+CP15.7 (7.2–27.0)Overall D+CP0.64 (0.507–0.800)<0.000136.1 (29.3–42.9) PBO+CP18.1 (13.0–23.9)MMRp/MSSaNo hypothesis testing of PFS in MMRp/MSS was planned. Maturity: D+CP0.76 (0.592–0.981) NA28.4 (21.2–36.0) PBO+CP18.8 (12.8–25.7)OSOverallb≈33%. D+CP0.64 (0.464–0.870)0.0021eP-value ≤0.00177 required for statistical significance at this analysis.71.3 (64.5–77.1) PBO+CP56.0 (48.9–62.5)dMMR/MSI-Hc≈26%. D+CP0.30 (0.127–0.699) NA83.3 (66.8–92.0) PBO+CP58.7 (43.4–71.2)MMRp/MSSd≈36%. D+CP0.73 (0.515–1.024) NA67.7 (59.8–74.4) PBO+CP55.1 (46.8–62.5)a No hypothesis testing of PFS in MMRp/MSS was planned. Maturity:b ≈33%.c ≈26%.d ≈36%.e P-value ≤0.00177 required for statistical significance at this analysis. Open table in a new tab D+CP showed statistically significant and clinically meaningful PFS benefits in the dMMR/MSI-H and overall populations vs CP alone. A clinically relevant benefit in PFS was also observed in the MMRp/MSS population. An early trend toward improved OS was observed in all populations. The combination of dostarlimab+CP represents a new SOC for pts with newly diagnosed primary A/R EC.