KEY TAKEAWAYS
- This Phase III study evaluated durvalumab with paclitaxel/carboplatin + bevacizumab, then maintenance durvalumab, bevacizumab + olaparib in newly diagnosed AOC pts without a tumor BRCA1/2 Mutation.
- The primary endpoint was PFS in Arm 3 versus Arm 1, first in the non-tBRCAm HRD+ cohort and then in the ITT populations.
- The study showed an enhanced progression-free survival in new ovarian cancer patients with triple therapy combination.
The Phase III DUO-O study involved newly diagnosed pts with high-grade epithelial non-tumour (t) BRCAm advanced ovarian cancer (AOC). They underwent primary or planned interval debulking surgery and received one cycle of a regimen involving paclitaxel/carboplatin +/- bevacizumab.
Starting from Cycle 2, pts were randomized in 1:1:1 to three treatment arms. Arm 1 involved paclitaxel/carboplatin + bevacizumab + a placebo, followed by maintenance bevacizumab for 15 months and placebos for 24 months. In Arm 2, pts were given paclitaxel/carboplatin + bevacizumab + durvalumab and then switched to a maintenance regimen of bevacizumab + durvalumab + placebo. Arm 3 included paclitaxel/carboplatin + bevacizumab + durvalumab, followed by maintenance bevacizumab + durvalumab + olaparib.
The primary endpoint was progression-free survival (PFS) in Arm 3 versus Arm 1, first in the non-tBRCAm HRD+ cohort, and then in the intent-to-treat (ITT) groups.
In a predetermined interim analysis, Arm 3 showed a notable improvement in PFS compared to Arm 1, with hazard ratios (HR) of 0.49 (95% CI 0.34–0.69; P<0.0001) in the HRD+ population and 0.63 (95% CI 0.52–0.76; P<0.0001) in the ITT population.
Additionally, a beneficial effect on PFS was observed in the HRD- subgroup, with an HR of 0.68 (95% CI 0.54–0.86). Arm 2 exhibited a numerical enhancement in PFS compared to Arm 1 in the ITT population, but this was not statistically significant.
Serious adverse events (AEs) were reported in 34%, 43%, and 39% of pts in Arms 1, 2, and 3, respectively.
In pts with newly diagnosed non-tBRCAm AOC, the regimen of paclitaxel/carboplatin + bevacizumab + durvalumab, followed by maintenance therapy with bevacizumab + durvalumab + olaparib, exhibited statistically significant and clinically meaningful enhancement in PFS compared to the regimen of paclitaxel/carboplatin + bevacizumab followed by maintenance bevacizumab. The safety of these treatment approaches aligned with the established safety profiles for each respective drug.
Source: https://ijgc.bmj.com/content/33/Suppl_3/A428.3.abstract
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03737643
Marth, C., Park-Simon, T-W., Aghajanian, C., Reuss, A., Nishio, S., Lim, M.C., Rubio-Pérez, M.J., Vardar, M.A., Scambia, G., Sabatier, R., Haslund, C., Colombo, N., Chudecka-Glaz, A., Lheureux, S., Huygh, G., Schochter, F., Wenham, R.M., Okamoto, A., Day, E., Harter, P. Durvalumab With Paclitaxel/Carboplatin + Bevacizumab Then Maintenance Durvalumab, Bevacizumab + Olaparib In Patients With Newly Diagnosed Advanced Ovarian Cancer Without A Tumour BRCA1/2 Mutation: Results From The DUO-O/ENGOT-Ov46/AGO-OVAR 23/GOG-3025 Trial.
