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 Merry Jennifer Markham, MD, FACP, FASCO ASCO Expert.
People with newly diagnosed advanced ovarian cancer without BRCA mutations, 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 only, according to the interim analysis of DUO-O, an international phase III randomized clinical trial.
Study at a Glance
|
Focus |
Effectiveness of a novel combination therapy approach for newly diagnosed advanced ovarian cancer. |
|
Population |
An international group of 1,130 patients with stage III or IV high-grade epithelial tumors that did not have BRCA mutations and were either homologous recombination deficiency (HRD) positive or negative (HRD is the inability to effectively repair double-strand DNA breaks). Patients had completed or were going to receive debulking surgery. |
|
Findings |
Patients were randomized to 1 of 3 arms. Patients in all arms received the standard of care - upfront paclitaxel/carboplatin chemotherapy plus bevacizumab, followed by maintenance bevacizumab. 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 show:
|
|
Significance |
The U.S. Food and Drug Administration has approved more ovarian cancer therapies since 2014 than in the 60 prior years combined. Relapse rates, however, remain high, averaging around two years. The increased PFS and reduction in risk of death seen with the addition of durvalumab and olaparib to the standard-of-care is a promising advance for these patients. |
Key Findings
In the trial, newly diagnosed patients with advanced high-grade epithelial ovarian cancer without BRCA mutations who received the standard of care (upfront paclitaxel/carboplatin and bevacizumab, plus maintenance bevacizumab) plus upfront durvalumab and maintenance durvalumab and olaparib had improvement in PFS compared to patients who received the standard of care. Of patients with HRD-positive tumors in the durvalumab + olaparib group, the risk of the disease progressing 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 + olaparib, the risk of the disease progressing was 37% less than for those who received the standard of care. In the durvalumab + olaparib arm, the risk of the disease progressing was 32% lower in all subsets of patients, including both HRD-positive and negative patients, compared to the standard-of-care arm.
“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 Philipp Harter, MD, PhD, director in the Department of Gynecology and Gynecologic Oncology at the Evangelische Kliniken Essen-Mitte hospital in Essen, Germany.
An estimated 19,710 new cases of ovarian cancer will be diagnosed in the United States in 2023, and an estimated 13,270 deaths due to the disease will occur. Only 20% of all cases of ovarian cancer are found early. When disease is detected at stage III or higher, survival rates can be as low as 30%. About half of the patients who are diagnosed with ovarian cancer are 63 years or older, and it is more common in White people than in Black people.1
About the Study
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, which blocks a certain cell-repair mechanism. Two recent studies have shown that maintenance olaparib benefits newly diagnosed patients with a BRCA mutation and that bevacizumab benefits patients with HRD-positive tumors. In patients with tumors that are HRD-positive, cancer cells have a harder time repairing themselves which means certain treatments, such as PARP inhibitors, are more likely to be effective. This led researchers to explore the novel combination of bevacizumab and durvalumab with the addition of olaparib to the maintenance therapy regimen to see if it would enhance the antitumor effect.
Next Steps
Researchers will formally assess overall survival and other secondary endpoints in a subsequent analysis.
