Background/rationale: In Part 1 of the phase 3 RUBY trial (NCT03981796; funding: GSK), DOST+CP significantly improved progression-free and overall survival in patients with pA/rEC. Time to first subsequent therapy (TFST) and second subsequent therapy (TSST) can offer insights on the regimen’s clinical benefit and its impact beyond first progression.
Methods: Patients were randomized 1:1 to receive DOST+CP or PBO+CP Q3W (6 cycles) followed by DOST or PBO monotherapy Q6W for ≤3 years (target accrual: 470 patients). Post-hoc second interim TFST and TSST analyses were performed in the overall, mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H), and mismatch repair proficient/microsatellite stable (MMRp/MSS) populations (data cutoff: 22/09/2023). TFST and TSST: time from randomization to the date of the first dose of first or second subsequent anticancer therapy after study drug, respectively, or death by any cause, whichever occurred first.
Results: Of 494 randomized patients (DOST+CP: n=245; PBO+CP: n=249), 118 were dMMR/MSI-H (n=53; n=65) and 376 were MMRp/MSS (n=192; n=184). Median TFST and TSST were longer with DOST+CP than PBO+CP in the overall population (15.3 vs 10.2 months, hazard ratio [HR] 0.63, 95% CI 0.51-0.78 and 31.3 vs 19.9 months, HR 0.67, 95% CI 0.53-0.85, respectively), dMMR/MSI-H population (not reached [NR] vs 10.5 months, HR 0.34, 95% CI 0.20-0.57 and NR vs 24.0 months, HR 0.41, 95% CI 0.23-0.74, respectively) and MMRp/MSS population (12.7 vs 10.2 months, HR 0.73, 95% CI 0.58-0.92 and 26.8 vs 18.7 months, HR 0.73, 95% CI 0.57-0.94, respectively).
Conclusion: Prolonged TFST and sustained benefits through TSST with DOST+CP vs PBO+CP were reported across the overall, dMMR/MSI-H, and MMRp/MSS populations in the RUBY trial, supporting the frontline use of DOST+CP in all patients with pA/rEC.
© 2025 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and presented at the 2025 ASCO Annual Meeting. All rights reserved.