KEY TAKEAWAYS
- The DUO-O phase 3 trial aimed to report updated results on significant PFS benefit with D+CP+B vs CP+B in patients with GC.
- The results revealed improved PFS and PFS2 with a favorable OS trend in non-tBRCAm HRD+ and ITT populations.
The DUO-O phase III, placebo-controlled study demonstrated a statistically significant and clinically meaningful progression free survival (PFS) benefit with Durvalumab+ carboplatin/paclitaxel + bevacizumab (D+CP+B) followed by D+B+ olaparib (O) maintenance (mtx) compared to CP+B followed by B in non-tumour BRCA1/BRCA2 mutation (tBRCAm) HRD+ and non-tBRCAm ITT populations (primary endpoint; Harter JCO 2023;41:17; LBA5506).
Fabian Trillsch and the team aimed to present the updated results on the DUO-O phase 3 study.
Patients with newly diagnosed high-grade epithelial advanced ovarian cancer (AOC) and primary or planned interval debulking surgery were included. Following one cycle of CP ± B, patients with non-tBRCAm AOC were randomized 1:1:1, stratified by timing and outcome of cytoreductive surgery (no macroscopic residual disease after upfront primary surgery and all others) and geographic region (North America, Europe, and other regions), into 3 arms that were Arm 1 (control) received CP + B followed by B; Arm 2 received D + CP + B followed by D + B; and Arm 3 received D + CP + B followed by D + B + O mtx.
Final descriptive PFS and subgroup analyses (Arm 3 vs. Arm 1), secondary endpoints of PFS (Arm 2 vs. Arm 1; non-tBRCAm ITT), interim OS (both formally tested per the predefined multiple testing procedure), and PFS2 were presented.
The results revealed that at DCO2 (18 Sep 2023), the PFS benefit for Arm 3 compared to Arm 1 was sustained in both the non-tBRCAm HRD+ and non-tBRCAm ITT populations. This benefit remained consistent across preplanned subgroups, including for the stratification factors. The interim OS analysis for Arm 3 versus Arm 1 (non-tBRCAm ITT) did not show statistical significance.
However, a favorable OS trend was observed for Arm 3 compared to Arm 1 in the non-tBRCAm HRD+ population. Additionally, in both populations, PFS2 was improved for Arm 3 compared to Arm 1 and Arm 2 compared to Arm 1. Safety findings at DCO2 were similar to those observed at DCO1.
The study concluded that D+CP+B followed by D+B+O mtx consistently improved PFS across all subgroups compared to the control group. In the non-tBRCAm HRD+ population, median PFS reached 45.1 months, the longest observed in this patient cohort within the first-line setting to date, accompanied by a favorable trend in OS. Additionally, PFS2 showed improvement in both the non-tBRCAm HRD+ and non-tBRCAm ITT populations.
The trial is sponsored by the AstraZeneca.
Source: https://cslide.ctimeetingtech.com/gynae24hybrid/attendee/confcal/show/session/21
Clinical Trial: https://clinicaltrials.gov/study/NCT03737643
Trillsch F, Okamoto A, Kim JW, et al. (2024). “Durvalumab (D) + carboplatin/paclitaxel (CP) + bevacizumab (B) followed by D, B + olaparib (O) maintenance (mtx) for newly diagnosed advanced ovarian cancer (AOC) without a tumour BRCA1/BRCA2 mutation (non-tBRCAm): Updated results from DUO-O.” Presented at ESMO GC 2024. (Abstract 43O)
