Durvalumab plus paclitaxel/carboplatin and bevacizumab followed by maintenance bevacizumab with durvalumab and olaparib significantly improves progression-free survival (PFS) vs paclitaxel/carboplatin with bevacizumab followed by maintenance bevacizumab in patients with newly diagnosed ovarian cancer without a BRCA1/2 mutation.

These findings, from the DUO-O trial, were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting by lead author Philipp Harter, MD, PhD, Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, and AGO, Essen, Germany.

Patients eligible for the trial had newly diagnosed FIGO stage 3 or 4, high-grade epithelial, advanced ovarian cancer without a tumor BRCA1/2 mutation and had completed upfront, or were planned to receive interval, debulking surgery and 1 cycle of paclitaxel/carboplatin with or without bevacizumab.

A total of 1130 patients were randomized in a 1:1:1 ratio to Arm 1, Arm 2, and Arm 3. Arm 1 received paclitaxel/carboplatin with bevacizumab (15 mg/kg IV every 3 weeks) and durvalumab placebo (up to 6 cycles) followed by maintenance bevacizumab (15 mg/kg IV every 3 weeks; total 15 months) with durvalumab placebo (total 24 months) and olaparib placebo (total 24 months). Arm 2 received paclitaxel/carboplatin with bevacizumab and durvalumab (1120 mg IV every 3 weeks) followed by maintenance bevacizumab with durvalumab (1120 mg IV every 3 weeks) and olaparib placebo. Arm 3 received paclitaxel/carboplatin with bevacizumab and durvalumab followed by maintenance  bevacizumab with durvalumab and olaparib (300 mg tablets twice a day). 

The primary trial end point was PFS (modified RECIST 1.1 per investigator) in Arm 3 vs Arm 1 and was first tested in the patient population without a tumor BRCA1/2 mutation and HRD-positive population (GIS ≥42, Myriad MyChoice CDx) and then the intent-to-treat (ITT) population.

At a prespecified interim analysis, a statistically significant improvement in PFS was observed in Arm 3 vs Arm 1 in the homologous repair deficiency (HRD)-positive (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.34 to 0.69; P <.0001) and ITT populations (HR, 0.63; 95% CI, 0.52 to 0.76; P <.0001). In addition, a consistent PFS effect was observed in the HRD-negative subgroup (HR, 0.68; 95% CI, 0.54 to 0.86). While a numerical improvement in PFS was observed for Arm 2 vs Arm 1 (ITT population), statistical significance was not reached. During the trial, serious adverse events were reported in 34%, 43%, and 39% of patients in Arms 1, 2 and 3, respectively.

Source:

Harter P, Trillsch F, Okamoto A, et al. Durvalumab with paclitaxel/carboplatin (PC) and bevacizumab (bev), followed by maintenance durvalumab, bev, and olaparib in patients (pts) with newly diagnosed advanced ovarian cancer (AOC) without a tumor BRCA1/2 mutation (non-tBRCAm): Results from the randomized, placebo (pbo)-controlled phase III DUO-O trial. Presented at 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract LBA5506