First-line durvalumab plus carboplatin/paclitaxel and bevacizumab followed by durvalumab, bevacizumab plus olaparib maintenance significantly improves progression-free survival (PFS) in patients with newly diagnosed non-BRCA-mutated advanced ovarian cancer, when compared with carboplatin/paclitaxel and bevacizumab followed by bevacizumab, as shown in the DUO-O study.
“Overall, the DUO-O study demonstrated statistically significant clinical activity with durvalumab, chemotherapy, and bevacizumab followed by durvalumab, bevacizumab, and olaparib maintenance vs control,” the researchers said.
A total of 1,130 patients were included in the study. Following one cycle of carboplatin/paclitaxel ± bevacizumab, those without a tumour BRCA mutation (non-tBRCAm) were randomized at cycle 2 to carboplatin/paclitaxel plus bevacizumab followed by bevacizumab (control); carboplatin/paclitaxel, bevacizumab plus durvalumab followed by bevacizumab plus durvalumab (durvalumab arm); or carboplatin/paclitaxel, bevacizumab plus durvalumab followed by bevacizumab, durvalumab plus olaparib (durvalumab + olaparib arm).
The durvalumab + olaparib arm showed significantly better PFS than the control arm in the non-tBRCAm homologous recombination deficiency (HRD)-positive (median PFS 37.3 vs 23.0 months; hazard ratio [HR], 0.49, 95 percent confidence interval [CI], 0.34‒0.69; p<0.0001) and the non-tBRCAm intention-to-treat (ITT) populations (median PFS 24.2 vs 19.3 months; HR, 0.63, 95 percent CI, 0.52‒0.76; p<0.001). [Ann Oncol 2026;37:503-520]
PFS was numerically higher in the durvalumab arm relative to the control arm in the non-tBRACm ITT population (median PFS 20.6 vs 19.3 months; HR, 0.87, 95 percent CI, 0.73‒1.04; p=0.13).
The final PFS and interim overall survival (OS) analysis revealed consistent PFS results, while the OS for the durvalumab + olaparib arm, compared with the control arm, had an HR of 0.95 (95 percent CI, 0.76‒1.20; p=0.68; 39.0 percent maturity) in the non-tBRCAm ITT population.
“DUO-O met its primary endpoints, demonstrating a statistically significant PFS improvement in the durvalumab + olaparib arm which was clinically meaningful vs control in both the non-tBRCAm HRD-positive and non-tBRCAm ITT populations,” the researchers said.
“Safety was generally consistent with the profiles of the individual agents,” they added.
Previous trials
The recent KEYLYNK-001 phase III trial, which examined a combination of immunotherapy (pembrolizumab), olaparib, and optional bevacizumab, reported a significant improvement in PFS (HR, 0.68, 95 percent CI, 0.58‒0.81). The addition of pembrolizumab to SOC, however, did not improve PFS regardless of PD-L1 expression and OS across the study group. [Int J Gyn Cancer 2025;35:101704]
Likewise, in the FIRST-ENGOT-OV44 phase III trial, the addition of dostarlimab to standard carboplatin-paclitaxel chemotherapy and niraparib maintenance, with or without bevacizumab, resulted in a significant PFS improvement, but no difference was noted in OS. [Int J Gyn Cancer 2025;35:101704]
“Distinguishing features include the agent combinations, with DUO-O being the only study mandating bevacizumab use; and study design, where DUO-O included formal testing in the HRD-positive population per multiple testing procedure,” the researchers said.
Patient selection also varied based on BRCA mutation. FIRST-ENGOT-OV44 included both BRCAm and BRCA wild-type patients, while KEYLINK-001 only included BRCA wild-type individuals. In DUO-O, non-tBRCAm patients were assigned to a separate group.
“Taken together, these are important factors that should be considered carefully when interpreting the results of the DUO-O study within the context of other phase III trials combining immunotherapy and poly (ADP-ribose) polymerase inhibitors in ovarian cancer,” the researchers said.