DUO-E: trial | Bending the Curve: Trial by Trial

DUO-E

Durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab with or without olaparib as first-line treatment for advanced or recurrent endometrial cancer (DUO-E/GOG-3041/ENGOT-EN10)

Phase 3N = 718NCT04269200

Population

Newly diagnosed advanced (FIGO stage III measurable or stage IV) or recurrent epithelial endometrial cancer, sarcomas excluded; previous systemic therapy only if adjuvant with at least 12 months to relapse; MMR status known before randomisation; about 80% pMMR in each arm

Design

Double-blind, placebo-controlled phase 3 trial, randomised 1:1:1. Carboplatin (AUC 5 or 6) and paclitaxel 175 mg/m2 every 3 weeks for 6 cycles with durvalumab 1120 mg or placebo, then maintenance durvalumab 1500 mg or placebo every 4 weeks with olaparib 300 mg twice daily or placebo tablets. Stratified by MMR status, disease status and region. ClinicalTrials.gov lists 805 participants; the JCO paper reports 718 randomised.

Primary endpoint

PFS

Arms

Placebo plus carboplatin-paclitaxel, then placebo (control, n = 241): Carboplatin and paclitaxel 175 mg/m2 with durvalumab placebo for 6 cycles, then durvalumab placebo and olaparib placebo
Durvalumab plus carboplatin-paclitaxel, then durvalumab (experimental, n = 238): Carboplatin and paclitaxel 175 mg/m2 with durvalumab 1120 mg for 6 cycles, then durvalumab 1500 mg every 4 weeks with olaparib placebo
Durvalumab plus carboplatin-paclitaxel, then durvalumab plus olaparib (experimental, n = 239): Carboplatin and paclitaxel 175 mg/m2 with durvalumab 1120 mg for 6 cycles, then durvalumab 1500 mg every 4 weeks with olaparib 300 mg twice daily

People

Westin SN, DUO-E/GOG-3041/ENGOT-EN10

PFSHR 0.71 (95% CI 0.57–0.89)Δ median PFS+0.6 monthsPFSHR 0.55 (95% CI 0.43–0.69)Δ median PFS+5.5 monthsPFSHR 0.42 (95% CI 0.22–0.80)PFSHR 0.41 (95% CI 0.21–0.75)

Show the numbers

Results reported for DUO-E
Endpoint	Analysis	Durvalumab plus carboplatin-paclitaxel, then durvalumab / Durvalumab plus carboplatin-paclitaxel, then durvalumab plus olaparib	Placebo plus carboplatin-paclitaxel, then placebo	Effect
PFSIntention-to-treat population (N = 718)Investigator-assessed progression-free survival (RECIST 1.1)	primaryWestin 2024	median 10.2 months	median 9.6 months	HR 0.71 (95% CI 0.57–0.89)P=0.003312 PFS events (65% maturity) for this comparison. Curves overlapped until about 6 months; the test for non-proportional hazards gave P = 0.018, so the hazard ratio is an average estimate.
PFSIntention-to-treat population (N = 718)Investigator-assessed progression-free survival (RECIST 1.1)	primaryWestin 2024	median 15.1 months	median 9.6 months	HR 0.55 (95% CI 0.43–0.69)P<0.0001299 PFS events (62% maturity) for this comparison. Non-proportional hazards test P = 0.03.
PFSdMMR subgroup (prespecified exploratory analysis)Investigator-assessed progression-free survival (RECIST 1.1)	exploratoryWestin 2024	—	median 7 months	HR 0.42 (95% CI 0.22–0.80)Median PFS was not reached in the durvalumab arm.
PFSdMMR subgroup (prespecified exploratory analysis)Investigator-assessed progression-free survival (RECIST 1.1)	exploratoryWestin 2024	median 31.8 months	median 7 months	HR 0.41 (95% CI 0.21–0.75)
PFSpMMR subgroup (prespecified exploratory analysis)Investigator-assessed progression-free survival (RECIST 1.1)	exploratoryWestin 2024	median 9.9 months	median 9.7 months	HR 0.77 (95% CI 0.60–0.97)
PFSpMMR subgroup (prespecified exploratory analysis)Investigator-assessed progression-free survival (RECIST 1.1)	exploratoryWestin 2024	median 15 months	median 9.7 months	HR 0.57 (95% CI 0.44–0.73)
OSIntention-to-treat population (N = 718)	interimWestin 2024	—	—	HR 0.77 (95% CI 0.56–1.07)P=0.120First interim analysis at about 28% maturity (199 deaths); not statistically significant.
OSIntention-to-treat population (N = 718)	interimWestin 2024	—	—	HR 0.59 (95% CI 0.42–0.83)P=0.003First interim analysis at about 28% maturity (199 deaths); the paper states that neither comparison reached statistical significance at this interim analysis.

Results reported for DUO-E
Endpoint	Analysis	Durvalumab plus carboplatin-paclitaxel, then durvalumab / Durvalumab plus carboplatin-paclitaxel, then durvalumab plus olaparib	Placebo plus carboplatin-paclitaxel, then placebo	Effect
PFSIntention-to-treat population (N = 718)Investigator-assessed progression-free survival (RECIST 1.1)	primaryWestin 2024	median 10.2 months	median 9.6 months	HR 0.71 (95% CI 0.57–0.89)P=0.003312 PFS events (65% maturity) for this comparison. Curves overlapped until about 6 months; the test for non-proportional hazards gave P = 0.018, so the hazard ratio is an average estimate.
PFSIntention-to-treat population (N = 718)Investigator-assessed progression-free survival (RECIST 1.1)	primaryWestin 2024	median 15.1 months	median 9.6 months	HR 0.55 (95% CI 0.43–0.69)P<0.0001299 PFS events (62% maturity) for this comparison. Non-proportional hazards test P = 0.03.
PFSdMMR subgroup (prespecified exploratory analysis)Investigator-assessed progression-free survival (RECIST 1.1)	exploratoryWestin 2024	—	median 7 months	HR 0.42 (95% CI 0.22–0.80)Median PFS was not reached in the durvalumab arm.
PFSdMMR subgroup (prespecified exploratory analysis)Investigator-assessed progression-free survival (RECIST 1.1)	exploratoryWestin 2024	median 31.8 months	median 7 months	HR 0.41 (95% CI 0.21–0.75)
PFSpMMR subgroup (prespecified exploratory analysis)Investigator-assessed progression-free survival (RECIST 1.1)	exploratoryWestin 2024	median 9.9 months	median 9.7 months	HR 0.77 (95% CI 0.60–0.97)
PFSpMMR subgroup (prespecified exploratory analysis)Investigator-assessed progression-free survival (RECIST 1.1)	exploratoryWestin 2024	median 15 months	median 9.7 months	HR 0.57 (95% CI 0.44–0.73)
OSIntention-to-treat population (N = 718)	interimWestin 2024	—	—	HR 0.77 (95% CI 0.56–1.07)P=0.120First interim analysis at about 28% maturity (199 deaths); not statistically significant.
OSIntention-to-treat population (N = 718)	interimWestin 2024	—	—	HR 0.59 (95% CI 0.42–0.83)P=0.003First interim analysis at about 28% maturity (199 deaths); the paper states that neither comparison reached statistical significance at this interim analysis.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
PFS	0.71	0.57–0.89
PFS	0.55	0.43–0.69
PFS	0.42	0.22–0.8
PFS	0.41	0.21–0.75
PFS	0.77	0.6–0.97
PFS	0.57	0.44–0.73
OS	0.77	0.56–1.07
OS	0.59	0.42–0.83

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Durvalumab plus carboplatin-paclitaxel, then durvalumab (experimental)
Placebo plus carboplatin-paclitaxel, then placebo (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Durvalumab plus carboplatin-paclitaxel, then durvalumab	Placebo plus carboplatin-paclitaxel, then placebo
0	100.0%	100.0%
6	66.5%	64.8%
13	41.3%	39.1%
19	27.5%	25.4%
26	17.1%	15.3%

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Durvalumab plus carboplatin-paclitaxel, then durvalumab plus olaparib (experimental)
Placebo plus carboplatin-paclitaxel, then placebo (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Durvalumab plus carboplatin-paclitaxel, then durvalumab plus olaparib	Placebo plus carboplatin-paclitaxel, then placebo
0	100.0%	100.0%
9	66.2%	52.2%
19	41.8%	25.4%
28	27.7%	13.2%
38	17.5%	6.4%

Appears in

2023 DUO-E: durvalumab with or without olaparib, first line

Sources

Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, et al. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024;42(3):283-299.
PubMed DOI