Dr Olawaiye on the Potential Role of Afuresertib Plus Paclitaxel in pAKT-Expressing Platinum-Resistant Ovarian Cancer

“It looks like [a] biomarker-selected subgroup might [achieve] …better efficacy from the afuresertib medication [compared with an all-comer population].”

Alexander B. Olawaiye, MD, a professor in the Department of Obstetrics & Reproductive Sciences at the University of Pittsburgh, as well as the director of gynecologic cancer research at Magee-Women’s Hospital of the University of Pittsburgh Medical Center, discussed the significance of findings from the phase 2 PROFECTA-II/GOG-3044 trial (NCT04374630) investigating afuresertib plus paclitaxel in patients with platinum-resistant ovarian cancer.

Findings from the trial, which were presented by Thomas J. Herzog, MD, of the University of Cincinnati College of Medicine, at the 2025 SGO Annual Meeting on Women’s Cancer, showed that treatment with afuresertib plus paclitaxel did not generate significant progression-free survival (PFS) or overall survival benefit vs paclitaxel monotherapy in patients with platinum-resistant ovarian cancer who had progressed on 1 to 5 prior chemotherapies. Patients in the intention-to-treat population achieved a median PFS of 4.3 months (95% CI, 3.58-5.62) with afuresertib plus paclitaxel vs 4.1 months (95% CI, 2.63-5.36) with paclitaxel alone (HR, 0.7; 95% CI, 0.5-1.10; P = .139).

However, an exploratory analysis showed a signal for improved outcomes in a biomarker-selected patient population. Among patients with pAKT expression levels above 1, the median PFS was 5.4 months (95% CI, 3.42-6.41) with the combination vs 2.9 months (95% CI, 1.25-not evaluable) with paclitaxel monotherapy (HR, 0.4; 95% CI, 0.12-1.00). Among patients with pAKT-negative disease, the median PFS in these respective populations was 4.4 months (95% CI, 2.83-6.97) vs 2.9 months (95% CI, 1.41-6.74; HR, 0.7 [95% CI, 0.39-1.27]).

In the future, investigators may try to replicate this trial in a biomarker-selected patient population, Olawaiye noted. Results from this study indicate that the combination of afuresertib and paclitaxel may be most effective for patients with pAKT-positive disease, although further research is necessary to confirm these findings, he concluded.