40MO First-line (1L) Durvalumab + Carboplatin/paclitaxel (CP) Followed by Durvalumab ± Olaparib for Endometrial Cancer (EC) (DUO-E): Objective Response Rate (ORR), Duration of Response (dor) and Time to Treatment Discontinuation or Death (TDT) by Mismatch Repair (MMR) Status

DUO-E showed statistically significant and clinically meaningful PFS benefit with CP + durvalumab followed by durvalumab ± olaparib v CP alone (primary endpoints); addition of olaparib conferred enhanced benefit in MMR proficient (pMMR) patients (pts). Pts with newly diagnosed FIGO Stage III (measurable disease [RECIST 1.1] before randomization) or IV, or recurrent EC, and naïve to systemic 1L treatment were randomized 1:1:1 to CP + durvalumab placebo (pbo; 6 cycles) followed by durvalumab pbo + olaparib pbo (CP arm); CP + durvalumab (1120 mg IV q3w) followed by durvalumab (1500 mg IV q4w) + olaparib pbo (CP+D arm); or CP + durvalumab followed by durvalumab + olaparib (300 mg bid; CP+D+O arm). ORR, DoR and TDT were assessed in ITT and MMR populations (exploratory). In the ITT at primary data cutoff (12 Apr 2023), ORRs with CP+D and CP+D+O were improved v CP (62 and 64 v 55%); median (m)DoR and mTDT were longer for CP+D v CP (mDoR: 13.1 [95% CI 6.0–NR] v 7.7 [5.1–13.5] months [mo]; mTDT: 9.9 [8.8–11.2] v 8.8 [7.6–9.7] mo) and further increased with CP+D+O (mDoR: 21.3 [8.1–29.9] mo; mTDT: 15.1 [12.5–18.6] mo; Table). In MMR deficient (dMMR) pts, CP+D and CP+D+O v CP improved ORRs (71 and 73 v 40%), mDoR (NR and 29.9 [95% CI 9.7–29.9] v 10.5 [4.6–NR] mo) and mTDT (21.2 [9.3–NR] and 20.6 [13.4–NR] v 6.7 [5.1–7.9] mo). In pMMR pts, ORRs were similar across arms but mDoR and mTDT were longer with CP+D v CP (mDoR: 10.6 [95% CI 5.6–NR] v 7.6 [5.1–13.1] mo; mTDT: 9.6 [8.1–10.6] v 9.3 [8.0–9.9] mo) and further extended with CP+D+O (mDoR: 18.7 [8.0–NR] mo; mTDT: 13.4 [10.6–15.6] mo). CP + durvalumab followed by durvalumab ± olaparib improved ORR, DoR and TDT v CP (ITT population). In dMMR pts, CP+D consistently improved ORR, DoR and TDT v CP. In pMMR pts, CP+D improved mDoR v CP and adding olaparib further extended mDoR and mTDT v CP+D.Table: 40MOITTdMMRpMMRCP n=241CP+D n=238CP+D+O n=239CP n=49CP+D n=46CP+D+O n=48CP n=192CP+D n=192CP+D+O n=191mTDT, mo (95% CI)8.8 (7.6–9.7)9.9 (8.8–11.2)15.1 (12.5–18.6)6.7 (5.1–7.9)21.2 (9.3–NR)20.6 (13.4–NR)9.3 (8.0–9.9)9.6 (8.1–10.6)13.4 (10.6–15.6)Pts with measurable disease at baseline, n198202184424237156160147Objective response, n (%)*109 (55)125 (62)117 (64)17 (40)30 (71)27 (73)92 (59)95 (59)90 (61)mDoR, mo (IQR)7.7 (5.1–13.5)13.1 (6.0–NR)21.3 (8.1–29.9)10.5 (4.6–NR)NR (22.0–NR)29.9 (9.7–29.9)7.6 (5.1–13.1)10.6 (5.6–NR)18.7 (8.0–NR)*In pts with measurable disease at baseline. CI, confidence interval; IQR, interquartile range; ITT, intent to treat; NR, not reached. Open table in a new tab