Durvalumab Plus Olaparib Improves Numerical OS in Advanced Endometrial Cancer

First-line carboplatin/paclitaxel plus durvalumab (Imfinzi) followed by maintenance durvalumab with or without olaparib (Lynparza) numerically improved overall survival (OS) vs carboplatin/paclitaxel alone in patients with advanced or recurrent endometrial cancer, but the difference did not reach statistical significance at the second interim analysis of the phase 3 DUO-E/GOG-3041/ENGOT-EN10 trial (NCT04269200) presented at the 2026 European Society for Medical Oncology (ESMO) Congress.¹

At a median follow-up of approximately 52 months in censored patients and an overall data maturity of 52.1%, the median OS was 51.1 months (95% CI, 44.2-not reached [NR]) in the durvalumab plus olaparib arm (n = 239) vs 39.6 months (95% CI, 30.3-49.2) in the control arm (n = 241; HR, 0.77; 95% CI, 0.60-0.98; P = .037).

The median OS was 40.7 months (95% CI, 34.7-57.9) in the durvalumab arm (n = 238; HR vs control, 0.87; 95% CI, 0.68-1.11; P = .259). Neither comparison crossed its prespecified significance threshold (2-sided P < .0165 and P < .0184, respectively).

The 36-month OS rates were 63.4%, 55.5%, and 52.0% in the durvalumab plus olaparib, durvalumab, and control arms, respectively. OS will be formally retested at the final analysis.

"Overall, these favorable interim OS and post-progression end points further support chemotherapy plus durvalumab followed by durvalumab or durvalumab and olaparib maintenance as treatments for advanced and recurrent endometrial cancer," Shannon N. Westin, MD, MPH, a professor of gynecologic oncology and reproductive medicine at The University of Texas MD Anderson Cancer Center, said in her ESMO 2026 presentation.

How was the phase 3 DUO-E trial of durvalumab with or without olaparib in endometrial cancer designed?

The global, double-blind, placebo-controlled trial enrolled 718 patients with newly diagnosed stage III or IV or recurrent endometrial cancer of any histology except sarcoma who had known mismatch repair status and had not received first-line systemic therapy, PARP inhibitors, or immunotherapy.

Patients were randomly assigned 1:1:1 to 6 cycles of carboplatin/paclitaxel followed by placebo maintenance (control arm), carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab (durvalumab arm), or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib. Randomization was stratified by mismatch repair status, disease status, and geographic region.

The dual primary end points were investigator-assessed progression-free survival (PFS) for each experimental arm vs control. OS was the key secondary end point; other secondary end points included time to first subsequent therapy or death (TFST), time to second subsequent therapy or death (TSST), time to treatment discontinuation or death, and safety.

Approximately 20% of patients in each arm had deficient mismatch repair (dMMR) tumors, and serous histology accounted for 22%, 24%, and 18% of the control, durvalumab, and durvalumab plus olaparib arms, respectively.

Primary analysis results published in the Journal of Clinical Oncology in 2024 showed that the trial met both primary end points.² The median PFS was 15.1 months with durvalumab plus olaparib and 10.2 months with durvalumab vs 9.6 months with control (HR, 0.55; 95% CI, 0.43-0.69; P < .0001; and HR, 0.71; 95% CI, 0.57-0.89; P = .003, respectively). At that time, interim OS data were approximately 28% mature. Ahead of the meeting, Westin noted that these interim OS results would be among the gynecologic oncology data to watch at ESMO 2026.³

How did OS and post-progression end points compare by mismatch repair status?

In the prespecified exploratory dMMR subpopulation (data maturity, 37.8%), the median OS was NR in both experimental arms vs 50.2 months (95% CI, 17.3-NR) in the control arm (n = 49), with HRs of 0.57 (95% CI, 0.30-1.05) for durvalumab (n = 46) and 0.43 (95% CI, 0.21-0.83) for durvalumab plus olaparib (n = 48).¹

In the proficient mismatch repair (pMMR) subpopulation (data maturity, 55.7%), the median OS was 45.8 months (95% CI, 37.1-58.7) with durvalumab plus olaparib (n = 191) and 38.3 months (95% CI, 26.3-54.5) with durvalumab (n = 192) vs 37.8 months (95% CI, 27.0-48.6) with control (n = 192), with HRs of 0.85 (95% CI, 0.65-1.11) and 0.95 (95% CI, 0.73-1.24), respectively.

In the overall population, the median TFST was 21.4 months, 13.6 months, and 10.8 months in the durvalumab plus olaparib, durvalumab, and control arms (HRs vs control, 0.61 and 0.79). The median TSST was 41.4 months, 27.2 months, and 25.8 months, respectively (HRs vs control, 0.74 and 0.91). Among patients with RECIST progression, subsequent immunotherapy was given to 27.6%, 30.6%, and 41.3% of patients, most commonly pembrolizumab (Keytruda) plus lenvatinib (Lenvima).

What was the safety profile of durvalumab with or without olaparib?

In the safety population, grade 3 or higher adverse effects (AEs) occurred in 69.7% of patients in the durvalumab plus olaparib arm (n = 238), 58.3% in the durvalumab arm (n = 235), and 57.2% in the control arm (n = 236); AEs led to discontinuation of any study treatment in 29.0%, 23.4%, and 19.1%, respectively.

The most common grade 3 or higher AEs were anemia (24.8%, 16.2%, and 14.4%), decreased neutrophil count (14.7%, 11.5%, and 15.3%), and neutropenia (11.5%, 8.5%, and 5.9%). Immune-mediated AEs occurred in 24.8%, 30.6%, and 6.8% of patients. No new cases of pure red cell aplasia or autoimmune hemolytic anemia were reported since the first data cutoff, and 1 case of myelodysplastic syndrome/acute myeloid leukemia occurred in the durvalumab plus olaparib arm.

Disclosures: Westin reported receiving grants or research support (all to institution) from AstraZeneca, AvengeBio, Bayer, Bio-Path, Clovis Oncology/Pharm&, Daiichi Sankyo, GSK, Jazz Pharmaceuticals, Loxo, Mereo, Novartis, Nuvectis, Pfizer, Roche/Genentech, and Zentalis; and receiving honoraria or consultation fees from AstraZeneca, Caris, Clovis Oncology/Pharma&, Corcept, Daiichi Sankyo, Eisai, EQRX, Gilead, GSK, Immunocore, ImmunoGen, Incyte, Lilly, Loxo, Merck, Mereo, Mersana, NGM Bio, Nuvectis, Pfizer, Roche/Genentech, SeaGen, Verastem, Vincerx, Zentalis, and ZielBio.

References

1. Westin SN, Moore K, Chon HS, et al. Durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib in advanced/recurrent endometrial cancer: interim overall survival and safety from the randomised phase 3 DUO-E/GOG-3041/ENGOT-EN10 study. Presented at: 2026 European Society for Medical Oncology Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA37.
2. Westin SN, Moore K, Chon HS, 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. doi:10.1200/JCO.23.02132
3. Long-Term and Novel ADC Data Dominate Top Gynecologic Cancer Abstracts at ESMO 2026. OncLive. Published October 14, 2026. Accessed October 24, 2026. https://www.onclive.com/view/long-term-and-novel-adc-data-dominate-top-gynecologic-cancer-abstracts-at-esmo-2026