Addition of Olaparib and Durvalumab to Standard of Care May Prolong Progression-Free Survival in Patients With Advanced Ovarian Cancer

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Patients with newly diagnosed advanced ovarian cancer without a BRCA mutation who received durvalumab and olaparib in addition to the standard of care had improved progression-free survival compared with those who received the standard of care alone, according to the interim analysis of DUO-O, an international phase III randomized clinical trial. The research was presented by Harter et al at the 2023 ASCO Annual Meeting (Abstract LBA5506).

The current standard of care includes chemotherapy (paclitaxel/carboplatin) and bevacizumab, an antiangiogenic agent. Durvalumab is a checkpoint inhibitor and olaparib is a PARP inhibitor. Two recent studies have shown that maintenance olaparib therapy may benefit newly diagnosed patients with a BRCA mutation and that bevacizumab therapy may benefit patients with homologous recombination deficiency (HRD)-positive tumors. This led researchers to explore the novel combination of bevacizumab and durvalumab with the addition of olaparib to the maintenance therapy regimen to see whether it would enhance the antitumor effect.

Key Findings in DUO-O

Patients were randomly assigned to one of three treatment arms. Patients in all arms received the standard of care: upfront paclitaxel/carboplatin chemotherapy plus bevacizumab, followed by maintenance bevacizumab therapy. For patients in arms 2 and 3, durvalumab was added to both the upfront and maintenance regimens. For patients in arm 3, olaparib was also added to the maintenance regimen.

Interim analysis results showed no significant difference in progression-free survival between the standard-of-care arm and the durvalumab arm. Progression-free survival was increased with the durvalumab-plus-olaparib arm compared with the standard-of-care arm. For HRD-positive patients, progression-free survival was 37.3 months vs 23 months for those in the standard-of-care arm. For patients in the intent-to-treat population, progression-free survival was 24.2 months in the olaparib arm vs 19.3 months for those in the standard-of-care arm.

In patients with HRD-positive tumors in the durvalumab-plus-olaparib group, the risk of disease progression was 51% less than for those who received the standard of care. In addition, for patients in the intent-to-treat group who received durvalumab plus olaparib, the risk of disease progression was 37% less than for those who received the standard of care. In the durvalumab-plus-olaparib arm, the risk of disease progression was 32% lower in all subsets of patients—including both HRD-positive and -negative patients—compared with the standard-of-care arm.

About 90% of patients completed the trial regimens. Serious adverse events were reported in 34% of patients in the standard-of-care arm, 43% of patients in the durvalumab arm, and 39% of patients in the olaparib arm.

Researchers will formally assess overall survival and other secondary endpoints in a subsequent analysis.  

“While there has been significant progress for patients with advanced ovarian cancer, an unmet need still remains. Our trial results provide encouraging evidence that we can find new treatment approaches for patients with advanced disease,” said presenting author Philipp Harter, MD, PhD, Director of the Department of Gynecology and Gynecologic Oncology at the Evangelische Kliniken Essen-Mitte hospital in Essen, Germany.

ASCO Perspective

“There is no early detection method for ovarian cancer, and over two-thirds of patients are diagnosed with advanced disease that frequently recurs. While more research is needed, this trial’s finding that a novel combination of therapies can prolong progression-free survival is indeed promising for patients with advanced ovarian cancer,” said ASCO expert Merry Jennifer Markham, MD, FACP, FASCO.

Disclosure: This study was funded by AstraZeneca. For full disclosures of the study authors, visit

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