Time to subsequent therapy in patients (pts) with primary advanced or recurrent endometrial cancer (pA/rEC) receiving dostarlimab plus carboplatin-paclitaxel (DOST+CP) compared with pts receiving placebo plus CP (PBO+CP) in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial.

Abstract

5601 Background: In Part 1 of the phase 3 RUBY trial (NCT03981796), DOST+CP significantly improved progression-free survival (PFS) and overall survival (OS) in pts with pA/rEC, leading to approval for frontline treatment in the US and the EU. Time to first subsequent therapy (TFST) and second subsequent therapy (TSST) can provide further insights on the clinical benefit of a regimen as well as any clinical impact beyond first progression. Methods: Pts were randomized 1:1 to receive DOST+CP or PBO+CP Q3W (6 cycles) followed by DOST or PBO monotherapy Q6W for ≤3 years. Primary endpoints were PFS and OS in the overall population and PFS in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) population. Post hoc TFST and TSST analyses were performed at the second interim analysis (data cut, Sept 22, 2023) in the overall, dMMR/MSI-H, and mismatch repair proficient/microsatellite stable (MMRp/MSS) populations. TFST and TSST were defined as the 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 pts randomized, 118 were dMMR/MSI-H and 376 were MMRp/MSS (Table). TFST and TSST were improved in all three populations. Median TFST was 5.1 and 2.5 mo longer in pts treated with DOST+CP vs PBO+CP in the overall and MMRp/MSS populations, respectively; median TFST was not reached (NR) in the DOST+CP arm of the dMMR/MSI-H population. Median TSST was extended by 11.4 and 8.1 mo in pts treated with DOST+CP vs PBO+CP in the overall and MMRp/MSS populations, respectively; median TSST was NR in the DOST+CP arm of the dMMR/MSI-H population. Hazard ratios favoring DOST+CP remained consistent between TFST and TSST in all populations evaluated. Conclusions: These results indicate prolonged TFST and sustained benefits through TSST with DOST+CP compared with PBO+CP across the overall, dMMR/MSI-H, and MMRp/MSS populations in the RUBY trial. Together with the statistically significant PFS and OS benefits, these findings support the frontline use of dostarlimab + CP as a standard of care in all pts with pA/rEC. Clinical trial information: NCT03981796 . Overall dMMR/MSI-H MMRp/MSS DOST+CP(n=245) PBO+CP(n=249) DOST+CP(n=53) PBO+CP(n=65) DOST+CP(n=192) PBO+CP(n=184) TFST, median (95% CI), mo 15.3 (12.3–20.1) 10.2 (9.1–10.9) NR(19.8–NR) 10.5(7.3–12.0) 12.7(11.4–17.1) 10.2(9.0–10.8) HR (95% CI) 0.63 (0.51–0.78) 0.34 (0.20–0.57) 0.73 (0.58–0.92) TSST, median (95% CI), mo 31.3(24.6–40.8) 19.9(16.3–23.1) NR(NR–NR) 24.0(16.1–39.1) 26.8(22.1–32.6) 18.7(15.3–22.0) HR (95% CI) 0.67 (0.53–0.85) 0.41 (0.23–0.74) 0.73 (0.57–0.94) NR, not reached; TFST, time to first subsequent treatment; TSST, time to second subsequent treatment.