mPFS approaches 4 years with 1L durvalumab- and olaparib-incorporating 5-drug combo in aEOC

In patients with homologous recombination deficiency-positive (HRD+) advanced epithelial ovarian cancer (aEOC) harbouring BRCA wild-type tumours, integrating durvalumab induction and durvalumab plus olaparib maintenance into first-line (1L) bevacizumab-containing chemotherapy significantly extends progression-free survival (PFS) and second PFS (PFS2), suggest updated results from the phase III DUO-O trial.

Specifically, the median PFS (mPFS) was 45.1 months with frontline durvalumab, carboplatin-paclitaxel (CP), and bevacizumab, followed by maintenance with durvalumab, bevacizumab, and olaparib, vs 23.3 months with CP plus bevacizumab, followed by single-agent bevacizumab maintenance (hazard ratio [HR], 0.46, 95 percent confidence interval [CI], 0.33–0.65). [ESMO Gyn 2024, abstract 43O]

Aside from a 1.8-year extension, the nearly 4-year mPFS observed with the 5-drug regimen (3.8 years) is “the longest in the 1L setting reported to date in patients with non–tumour BRCA-mutated (non-tBRCAm) HRD+ advanced OC,” said Professor Fabian Trillsch from the Department of Obstetrics and Gynecology at the University Hospital, LMU Munich in Munich, Germany.

The median PFS2 (mPFS2) had not yet been reached with the durvalumab-olaparib regimen vs 42 months with CP plus bevacizumab alone, resulting in a 38 percent lower risk of a PFS2 event in favour of the former vs the latter (HR, 0.62, 95 percent CI, 0.40–0.95).

Final planned PFS analysis

DUO-O consists of an ongoing three-arm trial evaluating two durvalumab-based regimens in 1,130 patients with newly diagnosed FIGO^* stage III–IV high-grade EOC. Either a primary debulking surgery had been performed or an interval debulking surgery was planned. All randomized patients have tumours that do not harbour BRCA1/BRCA2 mutations (ie, non-tBRCAm), and among them, 38.1 percent are HRD+.

The other durvalumab-based arm was treated with a regimen equivalent to the quintuple combination but without olaparib during maintenance. This arm did not contribute to the primary endpoint analysis.

The arm not treated with durvalumab or olaparib serves as a common control for the other two durvalumab-based arms.

The dosing and duration of CP and bevacizumab across the arms followed the GOG-0218 protocol, except that carboplatin may also be dosed at an area under the curve of 5. [N Engl J Med 2011;365:2473-2483] Treatments with durvalumab and olaparib lasted for 24 months, unless disease progressed or other discontinuation criteria were met.

The primary endpoints were investigator-assessed PFS in the durvalumab-olaparib regimen arm vs the control arm in the HRD+ population, and secondly, in the intention-to-treat (ITT) population.

The current final planned PFS analysis had the data cutoff extended by an additional 9.4 months vs the previously reported PFS interim analysis. [ASCO 2023, abstract LBA5506]

Non-tBRCAm ITT population

In the ITT population, which also included HRD-negative patients, PFS remained significantly improved with the quintuple regimen vs control (median, 25.1 vs 19.3 months; HR, 0.61, 95 percent CI, 0.51–0.73).

However, ITT PFS2 was not extended by a slight margin of significance (median, 35.4 vs 32.6 months; HR, 0.82, 95 percent CI, 0.67–1.01).

This data cutoff also served as an interim overall survival (OS) analysis; however, no definitive findings could be drawn for either population, as the maturity for OS events remained below 40 percent.

“DUO-O is ongoing, and further insights into the long-term benefits of the combination will be provided with additional follow-up,” concluded Trillsch.