Background
DUO-E was a phase III, three-arm RCT evaluating addition of durvalumab (anti-PD-L1) with or without olaparib maintenance to standard platinum-based chemotherapy in newly diagnosed advanced or recurrent endometrial cancer.
Interventions and follow up
Arm A (control): Carboplatin + paclitaxel ×6 → placebo maintenance
Arm B: Carboplatin + paclitaxel + durvalumab ×6 → durvalumab maintenance
Arm C: Carboplatin + paclitaxel + durvalumab ×6 → durvalumab + olaparib maintenance
Primary endpoint: PFS for Arm B vs A and Arm C vs A
mFollow-up: 15.0mo
Arm B: Carboplatin + paclitaxel + durvalumab ×6 → durvalumab maintenance
Arm C: Carboplatin + paclitaxel + durvalumab ×6 → durvalumab + olaparib maintenance
Primary endpoint: PFS for Arm B vs A and Arm C vs A
mFollow-up: 15.0mo
Results
mPFS Arm B vs A (overall): 10.2 vs 9.6mo (HR 0.71, 95% CI 0.57–0.89, P=.003)
mPFS Arm C vs A (overall): 15.1 vs 9.6mo (HR 0.55, 95% CI 0.43–0.69, P<.001)
dMMR Arm C vs A: mPFS NR vs 7.0mo (HR 0.37, 95% CI 0.21–0.63)
pMMR Arm C vs A: mPFS 9.6 vs 9.9mo (HR 0.66, 95% CI 0.50–0.87)
OS: immature
mPFS Arm C vs A (overall): 15.1 vs 9.6mo (HR 0.55, 95% CI 0.43–0.69, P<.001)
dMMR Arm C vs A: mPFS NR vs 7.0mo (HR 0.37, 95% CI 0.21–0.63)
pMMR Arm C vs A: mPFS 9.6 vs 9.9mo (HR 0.66, 95% CI 0.50–0.87)
OS: immature
Adverse events
Overall (grade ≥3): 56% (A), 67% (B), 78% (C); AE-related discontinuation 31% (C) vs 9% (A)
Hematologic (Arm C vs A): anemia 35% vs 10%, neutropenia 28% vs 22%, plus nausea. Immune-mediated AEs consistent with the durvalumab profile.
Hematologic (Arm C vs A): anemia 35% vs 10%, neutropenia 28% vs 22%, plus nausea. Immune-mediated AEs consistent with the durvalumab profile.
Conclusions
Both durvalumab alone and durvalumab + olaparib maintenance significantly improved PFS versus placebo in advanced/recurrent endometrial cancer, with the greatest benefit in dMMR/MSI-H tumors receiving doublet maintenance.
Key Limitations
Trial not powered for direct Arm B vs Arm C comparison, so the incremental value of adding olaparib in dMMR (where durvalumab alone is highly effective) is uncertain. Olaparib's contribution appears concentrated in the pMMR subset. OS immature; added toxicity and discontinuation with the triplet are substantial.
Clinical Context
FDA approved durvalumab with carboplatin/paclitaxel then maintenance durvalumab for dMMR primary advanced/recurrent endometrial cancer (June 2024); the durvalumab + olaparib combination has advanced toward approval for pMMR disease. Alongside NRG-GY018 (pembrolizumab) and RUBY (dostarlimab), DUO-E established chemo-immunotherapy as first-line standard, with MMR status guiding regimen choice.