Chemotherapy plus durvalumab, bevacizumab, and olaparib fails to provide OS benefit in newly diagnosed non-tBRCA mutated ovarian cancer

Based on final OS data from the Phase 3 DUO-O/ENGOT-ov46/GOG-3025 trial (NCT03737643) submitted in 2025, platinum-based therapy in patients with newly diagnosed non-tBRCA- mutated ovarian cancer Chemotherapy plus durvalumab/Infinifer, bevacizumab, and olaparib maintained a statistically significant and clinically meaningful improvement in median progression-free survival (PFS) compared with chemotherapy and bevacizumab but did not provide a significant overall survival (OS) benefit.

At a median follow-up of 56 months, results at the third data cutoff showed that in the intention-to-treat (ITT) population, patients receiving durvalumab, bevacizumab, and Median progression-free survival in patients with nontBRCA mutated disease (3 group; n=378) treated with lapalib chemotherapy was 25.1 months compared with patients who received chemotherapy and bevacizumab (group 1; n=375; HR , 0.62; 95%CI, 0.52-0.73) is 19.3 months. Patients who received chemotherapy plus bevacizumab and durvalumab (group 2, n=374) had a median progression-free survival of 20.6 months, which was longer than that in group 1 group had an advantage (HR, 0.84; 95%CI, 0.71-0.99). The PFS rates of 24 months and 48 months in group 3 were 53% and 30% respectively; in group 3 These corresponding rates were 39% and 22% in the n>2 group, and 33% and 16% respectively in the 1 group.

However, the median OS in group 3 was 50.5 months, while that in group 1 was 49.6 months (< span>HR, 0.92; 95%CI, 0.75-1.11; P=0.378). Likewise, Chapter 2The median OS of the group was 48.5 months, with no significant benefit compared with the 1 group (HR, 0.97; 0.80-1.18; P=0.785). In the third group, the OS rates at 24 months and 48 months were 83% and 53% respectively; Chapter The corresponding rates for group 2 and group 1 were 81% and 51% and 80% and 51% respectively.

The DUO-O study met both primary endpoints at the data cutoff 1, in the HRD positive and ITT populations, in the 3 group and PFS in the >1 group was statistically significant and clinically relevant; this benefit was maintained at the data cutoff of 3 and the median follow-up was approximately 56 months. In the final OS analysis, the observed PFS benefit did not translate into a statistically significant OS improvement.

DUO-O was a double-blind, multicenter study examining durvalumab plus platinum chemotherapy and bevacizumab, followed by maintenance durvalumab and bevacizumab or durvalumab, bevacizumab, and olaparib, in patients with newly diagnosed advanced ovarian cancer. Patients also need to be at least 18 years old, or 20 years old if they are registered in Japan, have an ECOG performance status of 0 or 1, and maintain organ and bone marrow function.

Eligible patients were randomly assigned to group 1, 2 or 3 in a ratio of 1:1:1. During the chemotherapy phase, all patients received chemotherapy combined with bevacizumab; patients in the 2 and 3 groups also received durvalumab treatment. In the maintenance phase, patients in groups 1, 2, and 3 received bevacizumab, bevacizumab plus durvalumab, or bevacizumab plus durvalumab and olaparib, respectively. Maintenance therapy lasted 2 years.

The primary endpoint was investigator-assessed PFS in the 3 and 1 arms according to RECIST 1.1 criteria in the non-BRCA mutation HRD-positive and ITT populations. Key secondary endpoints include investigator-assessed PFS, OS, and safety according to RECIST 1.1 criteria in the 2 and 1 cohorts in the non-BRCA mutated ITT population.

Additional efficacy findings at the DUO-O data cutoff 3 showed that the median PFS for patients in cohort 3 (n=140) with non-tBRCA mutated, HRD-positive disease was 45.1 months, while the 1 group was 23.3 months (n=143; HR, 0.49; 95%CI, 0.36-0.66). In group 2 (n=148), the median PFS was 25.6 months, compared with group 1 HR is 0.80 (95%CI, 0.60-1.05). In the third group, the progression-free survival rates at 24 months and 48 months were 73% and 47% respectively; in 2 In group 1, these corresponding rates were 52% and 31% respectively, and in group 1 they were 47% and 27% respectively.

In terms of OS in patients with non-tBRCA-mutated, HRD-positive disease, the 2 and 3 groups did not reach the median. Compared with the median OS of 66.8 months in the 1 group, patients in the 3 group had a 20% lower risk of death (HR, 0.80; 95%CI, 0.54-1.18; P=0.263), the mortality rate of patients in group 2 was reduced 16% (HR, 0.83; 95%CI0.57-1.23). In the third group, the OS rates at 24 months and 48 months were 96% and 71% respectively; Chapter The corresponding rates for group 2 and group 1 were 92% and 71%, 89% and 68% respectively.

Regarding safety, no adverse reactions (AE) of any grade were reported in Cohort 1 (99.2%), Cohort 2 (99.5%), and Cohort 3 (99.2%). Grade 3 or higher adverse events, adverse events leading to death, serious adverse events, immune-mediated adverse events, adverse events leading to dose adjustment, and adverse events leading to treatment discontinuation were reported in all 3 groups. Specific adverse events related to olaparib that occurred in all 3 groups included new primary malignancy and pneumonia.

Safety remains generally consistent with the known profile of each drug.

Reference: https://www.onclive.com/view/chemotherapy-plus-durvalumab-bevacizumab-and-olaparib-fails-to-offer-os-benefit-in-newly-diagnosed-non-tbrca-mutated-ovarian-cancer