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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)
Published: March 27, 2023
DOI: https://doi.org/10.1016/j.annonc.2023.02.008
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M.R. Mirza, D. Chase, B.M. Slomovitz, ... R.L. Coleman, M.A. Powell
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Background
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.
Methods
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/m2 Q3W (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.
Results
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.
Conclusions
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.
Clinical trial identification
NCT03981796.
Simultaneous publication in the New England Journal of Medicine
Mansoor R. Mirza, Dana M. Chase, Brian M. Slomovitz, et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med 2023; 23 March 2023. doi: 10.1056/NEJMoa2302312
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