Durvalumab with carboplatin/paclitaxel and bevacizumab followed by durvalumab and bevacizumab with or without olaparib maintenance in newly diagnosed non-BRCA-mutated advanced ovarian cancer

Harter, P.; Trillsch, F.; Okamoto, A.; Reuss, A.; Kim, J.-W.; Rubio-Pérez, M.J.; VARDAR, MEHMET; Scambia, G.; Trédan, O.; Nyvang, G.-B.; Colombo, N.; Bidziński, M.; Grimm, C.; Lheureux, S.; Van Nieuwenhuysen, E.; Heitz, F.; Wenham, R.M.; Nishio, S.; Lim, M.C.; Marquina, G.; Altundağ, Ö.; Bergamini, A.; Sabatier, R.; Wimberger, P.; Gold, M.A.; Sehouli, J.; Park-Simon, T.-W.; Kent, E.; Correa, A.; Aghajanian, C.

doi:10.1016/j.annonc.2025.11.020

Durvalumab with carboplatin/paclitaxel and bevacizumab followed by durvalumab and bevacizumab with or without olaparib maintenance in newly diagnosed non-BRCA-mutated advanced ovarian cancer

Harter P., Trillsch F., Okamoto A., Reuss A., Kim J., Rubio-Pérez M., ...Daha Fazla

Annals of Oncology, cilt.37, sa.4, ss.503-520, 2026 (SCI-Expanded, Scopus)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 37 Sayı: 4
Basım Tarihi: 2026
Doi Numarası: 10.1016/j.annonc.2025.11.020
Dergi Adı: Annals of Oncology
Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE
Sayfa Sayıları: ss.503-520
Anahtar Kelimeler: advanced ovarian cancer, bevacizumab, carboplatin/paclitaxel, durvalumab, non-tumor BRCA mutation, olaparib
Çukurova Üniversitesi Adresli: Evet

Özet

Background: Despite treatment advances in newly diagnosed advanced-stage ovarian cancer (aOC), improved outcomes are needed. Patients and methods: DUO-O (NCT03737643), a phase III placebo-controlled trial, enrolled patients with newly diagnosed aOC. Following one cycle of carboplatin/paclitaxel ± bevacizumab, patients without a tumor BRCA mutation (non-tBRCAm) were randomly assigned (1 : 1 : 1) at cycle 2 to carboplatin/paclitaxel plus bevacizumab followed by bevacizumab (control); carboplatin/paclitaxel, bevacizumab plus durvalumab followed by bevacizumab plus durvalumab (durvalumab arm); or carboplatin/paclitaxel, bevacizumab plus durvalumab followed by bevacizumab, durvalumab plus olaparib (durvalumab + olaparib arm). Investigator-assessed progression-free survival (PFS; primary endpoint) was tested for the durvalumab + olaparib arm versus control in the non-tBRCAm homologous recombination deficiency (HRD)-positive and non-tBRCAm intention-to-treat (ITT) populations. Results: One thousand one hundred and thirty patients were randomly allocated to the study. The prespecified interim PFS analysis [data cut-off (DCO): 5 December 2022] qualified as the primary analysis; PFS hazard ratio (HR) for the durvalumab + olaparib arm versus control was 0.49 [95% confidence interval (CI) 0.34-0.69, P < 0.0001; median (m) PFS 37.3 versus 23.0 months] in the non-tBRCAm HRD-positive and 0.63 (95% CI 0.52-0.76, P < 0.0001; mPFS 24.2 versus 19.3 months) in the non-tBRCAm ITT population. For the durvalumab arm versus control, PFS HR was 0.87 (95% CI 0.73-1.04, P = 0.13; mPFS 20.6 versus 19.3 months) in the non-tBRCAm ITT population. At final PFS and interim overall survival (OS) analysis (DCO: 18 September 2023), PFS results were consistent with primary analysis; interim OS HR for the durvalumab + olaparib arm versus control was 0.95 (95% CI 0.76-1.20, P = 0.68; 39.0% maturity) in the non-tBRCAm ITT population. Safety was generally consistent with the profiles of the individual agents. Conclusions: DUO-O met its primary PFS endpoints for first-line durvalumab plus carboplatin/paclitaxel and bevacizumab followed by durvalumab, bevacizumab plus olaparib maintenance versus carboplatin/paclitaxel and bevacizumab followed by bevacizumab in the non-tBRCAm HRD-positive and non-tBRCAm ITT populations. Further insight into long-term benefit is anticipated with additional follow-up.