Safety and tolerability of durvalumab + carboplatin/paclitaxel followed by durvalumab ± olaparib in patients with newly diagnosed advanced or recurrent endometrial cancer (EC) in the DUO-E/GOG-3041/ENGOT-EN10 trial.

5599 Background: DUO-E (NCT04269200) showed statistically significant and clinically meaningful progression-free survival improvement with addition of durvalumab (D) to carboplatin/paclitaxel (CP) followed by D ± olaparib (O) vs CP alone for patients (pts) with EC (Westin SN et al. J Clin Oncol 2024;42:283–99). We describe safety and tolerability, focusing on the most common adverse events (AEs). Methods: Pts with newly diagnosed FIGO Stage III/IV or recurrent EC and naïve to systemic treatment were randomized 1:1:1 to CP (CP + D placebo pbo; 6 cycles followed by D pbo + O pbo), CP+D (CP + D 1120 mg IV q3w; 6 cycles followed by D 1500 mg IV q4w + O pbo), or CP+D+O (CP + D 6 cycles followed by D + O 300 mg tablets bid). Safety was assessed through AEs. Results: 709 pts (19.3% mismatch repair deficient dMMR, 80.7% MMR proficient pMMR) received treatment (CP: n=236; CP+D: n=235; CP+D+O: n=238). Total median treatment duration with D/pbo was 9.0, 9.9 and 13.1 months in the CP, CP+D and CP+D+O arms and 5.7, 7.6 and 9.2 months withO/pbo, respectively. 18.6%, 20.9% and 24.4% of pts in the CP, CP+D and CP+D+O arm, respectively, had AEs leading to treatment discontinuations, 50.0%, 54.5% and 68.9% had AEs leading to dose interruptions, and 56.4%, 54.9% and 67.2% had grade ≥3 AEs. There was no increase in immune-mediated AEs or AEs of special interest for O with CP+D+O. There were 3 cases of pure red-cell aplasia with CP+D+O (all grade 3) and 3 of autoimmune hemolytic anemia (1 with CP+D, 2 with CP+D+O; all grade 3). The most common AEs were mostly low grade, with grade 3/4 in few pts (anemia 14%, 16%, 24% in the CP, CP+D, CP+D+O arms, respectively, alopecia 0%, 0%, 0%, nausea 1%, <1%, 3%, fatigue 2%, 2%, 2%), and led to few treatment discontinuations and interruptions (Table). AE profiles were generally consistent across MMR subgroups. Conclusions: In DUO-E, safety findings were generally consistent with the known safety profiles of CP, D and O. The addition of D to CP followed by D or by D + O resulted in expected and manageable safety profiles compared with CP alone, with the most common AEs being low grade and leading to few discontinuations or dose modifications/interruptions of D/pbo or O/pbo. Clinical trial information: NCT04269200 . Table: see text