38MO Progression-free survival (PFS) in primary advanced or recurrent endometrial cancer (pA/rEC) in the overall and mismatch repair proficient (MMR/MSS) populations and in histological and molecular subgroups: Results from part 2 of the RUBY trial
Mansoor Raza Mirza, S. Ghamande, L.C. Hanker, Destin Black, Nicoline Raaschou‐Jensen, L. Gilbert, A. Oaknin, A.A. Secord, Antonella Savarese, Robert W. Holloway, R. Kristeleit, J. Buscema, Ingrid Boere, Sudarshan Sharma, Christine Gennigens, P. Ghatage, Kaitlin Yablonski, S. Stevens, Hanna Trukhan, Mary Anne Powell
Abstract
In Part 1 of the phase 3 RUBY trial (NCT03981796) in pA/rEC, patients (pts) receiving dostarlimab (dostar)/carboplatin-paclitaxel (CP) exhibited significant benefits in PFS and overall survival versus CP alone. Outcomes may be further improved by adding a poly(ADP-ribose) polymerase inhibitor (PARPi). Here we report results from Part 2 of RUBY of dostar/CP followed by dostar/niraparib (nira; a PARPi) maintenance therapy in pts with pA/rEC. Pts were randomized 2:1 to dostar 500 mg IV + CP Q3W for 6 cycles followed by dostar 1000 mg IV Q6W + nira (individualized starting dose of 200 or 300 mg) PO daily for ≤3 years from randomization or to placebo (PBO) + CP Q3W for 6 cycles followed by PBOs for ≤3 years. The primary endpoint was PFS in the overall and MMRp/MSS populations. 291 pts were randomized (192 dostar/CP + dostar/nira; 99 PBO/CP). PFS was significantly improved in pts receiving dostar/CP + dostar/nira vs PBO/CP in the overall and MMRp/MSS populations (Table). In pts with endometrioid carcinoma, pts with other histologies, and across most biomarker subgroups (eg, TP53mut), the hazard ratio (HR) directionally favored dostar/CP + dostar/nira in the overall and MMRp/MSS populations. The safety profile observed was consistent with those of the individual agents.Table: 38MOPFSDostar/CP+dostar/niraPBO/CP+PBOHR (95% CI)Overall, n192990.60 (0.43–0.82) P=0.0007Median (95% CI), mo14.5 (11.8–17.4)8.3 (7.6–9.8)-MMRp/MSS, n142740.63 (0.44–0.91) P=0.0060Median (95% CI), mo14.3 (9.7–16.9)8.3 (7.6-9.8)-Pre-specified exploratory analysesNo. of pts with events/No. of ptsAll pts95/19269/99-Endometrioid carcinoma52/11446/670.58 (0.39–0.87)Other histologies42/7623/320.53 (0.32–0.88)Molecular subgroupbPOLεmut0/31/2-adMMR/MSI-H12/3710/170.45 (0.20–1.05)TP53mut27/3910/100.29 (0.13–0.63)No specific molecular profile37/7531/460.61 (0.38–0.99)Not evaluable19/3817/240.71 (0.37–1.37)a<20 events. bBased on whole exome sequencing. Open table in a new tab a<20 events. bBased on whole exome sequencing. RUBY Part 2 met its primary endpoint and is the first study to show significant and clinically meaningful improvement in PFS in the MMRp/MSS and overall populations. The trial is ongoing for OS follow-up. The safety profile observed was generally consistent with the known safety profiles of the individual agents. These data demonstrate a potential role for PARPi maintenance in pts receiving dostar/CP, especially for MMRp/MSS tumors.