Durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib as first-line treatment for endometrial cancer: Longitudinal changes in circulating tumor DNA.

• DOI: 10.1200/jco.2025.43.16_suppl.5512
• Publication Date: 2025-05-28T15:17:35Z
• Authors: Shannon Neville W...; Kathleen N. Moore; Michael Guy; Scott Jordan; Michael McHale; Eirwen Miller; Sobia Ozair; Kimberly Erin Res...; Molnár Szabolcs; Flora Zagouri; Pauline Wimberger; Lubomir Bodnar; Shoji Kamiura; Wang Wuliang; Conor Donnelly; Xiaochun Liu; Ross Stewart; Ying Wang; Sonia Iyer; Els Van Nieuwenhu...
• Keywords: Durvalumab; Carboplatin; Olaparib

5512 Background: DUO-E (NCT04269200) showed statistically significant and clinically meaningful progression-free survival (PFS) with carboplatin/paclitaxel (CP) plus durvalumab (D) followed by D (CP+D) ± maintenance olaparib (O) vs CP in endometrial cancer (intent-to-treat [ITT] population; primary endpoints). The greatest benefit for CP+D was mismatch repair deficient (dMMR) patients (pts); addition of O (CP+D+O) further enhanced PFS MMR proficient (pMMR) pts (prespecified exploratory analyses). We present longitudinal circulating tumor (ct)DNA analyses. Methods: Pts were randomized 1:1:1 to (CP alone), CP+D, or CP+D+O arms. ctDNA analyzed plasma at baseline (BL; Cycle 1 Day [C1D1]), during the chemotherapy phase (C3D1), prior initiation (C7D1), (C9D1) using methylation-based Guardant Infinity assay (Guardant Health, Palo Alto, CA). Results: Of 718 randomized, biomarker-evaluable population (BEP) comprised 347, 349, 350, 349 BL, C3D1, C7D1, C9D1, respectively. Pt characteristics similar ITT but fewer had Eastern Cooperative Oncology Group status 1. detectable 80% (278/347) C1D1 samples, presence BL associated shorter across treatment In both dMMR pMMR pts, led numerically greater reductions C3D1; continued lower detection C9D1 (Table) due a proportion switching from no (re-emergence) between C7D1 C9D1. limited effect on levels pts; however, rate increased clearance (CP+D+O CP+D: 48% 17%). Conclusions: this post hoc analysis, PFS. rapid less re-emergence maintenance. reduction reflecting an additional activity combination. Clinical trial information: NCT04269200 . rates (% [n/N]). Population Treatment arm C3D1 BEP 80 (94/118) 44 (51/117) 35 (41/117) 50 (58/117) 86 (96/112) 26 (29/112) 27 (30/112) 33 (37/112) 75 (88/117) 31 (37/120) 21 (26/121) 25 (30/120) 79 (11/14) 57 (8/14) (3/14) 43 (6/14) 91 (21/23) 23 (5/22) 32 (7/22) 22 (5/23) 85 (22/26) 41 (11/27) 18 (5/28) (6/27) (83/104) 42 (43/103) 37 (38/103) (52/103) 84 (75/89) (24/90) (23/90) 36 (32/89) 73 (66/91) 28 (26/93) (21/93) (24/93)