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