Durvalumab Regimen With Maintenance Olaparib Combo Improves PFS in Select High-Grade Epithelial Ovarian Cancer

Induction therapy with durvalumab (Imfinzi) plus chemotherapy and bevacizumab (Avastin), followed by maintenance with olaparib (Lynparza) plus durvalumab and bevacizumab, elicited a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with chemotherapy plus bevacizumab (Avastin) in patients with newly diagnosed advanced high-grade epithelial ovarian cancer who did not harbor BRCA mutations, according to data from an interim analysis of the phase 3 DUO-O trial (NCT03737643).¹

Additionally, findings for durvalumab plus chemotherapy and bevacizumab demonstrated a numerical improvement in PFS vs chemotherapy and bevacizumab alone; however, this arm did not reach statistical significance for PFS at the time of the analysis.

Data for overall survival (OS) and other secondary end points remained immature and will be formally assessed at a subsequent analysis. Full data from the interim analysis will be presented at upcoming medical meetings and shared with regulatory authorities.

“DUO-O showcases the power of academia and industry collaboration in advancing new treatment combinations for patients with ovarian cancer,” Philipp Harter, MD, PhD, director of the Department of Gynecology and Gynecologic Oncology at Evangelische Kliniken Essen-Mitte in Germany, and principal investigator for the trial, stated in a news release. “I’m grateful for the academic cooperative study groups and patients around the world that made this trial possible and look forward to sharing the results with the clinical community.”

The randomized, double-blind, placebo-controlled, multicenter DUO-O trial enrolled female patients at least 18 years of age with newly diagnosed, histologically confirmed, advanced stage III to IV high-grade epithelial ovarian cancer, including high-grade serous, high-grade endometroid, clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer, and/or fallopian-tube cancer.²

Patients were required to be candidates for cytoreductive surgery, either as up-front primary surgery, or have plans to undergo chemotherapy with interval debulking surgery; have evidence of presence or absence of BRCA1/2 mutation in tumor tissue; have an ECOG performance status of 0 or 1; and have preserved organ and bone marrow function.

Patients with non-epithelial ovarian cancer, borderline tumors, low-grade epithelial tumors, or mucinous histology were excluded. Other key exclusion criteria included prior systemic anti-cancer therapy for ovarian cancer, the inability to determine the presence or absence of a deleterious or suspected deleterious BRCAmutation, prior treatment with a PARP inhibitor or immune-mediated therapy, or planned intraperitoneal cytotoxic chemotherapy.

Investigators randomly assigned patients in a 1:1:1 fashion to induction therapy with platinum-based chemotherapy in combination with bevacizumab and placebo, followed by maintenance treatment with bevacizumab plus placebo (arm 1); induction therapy with platinum-based chemotherapy in combination with bevacizumab and durvalumab, followed by maintenance durvalumab and bevacizumab plus placebo (arm 2); or induction therapy with platinum-based chemotherapy in combination with bevacizumab and durvalumab, followed by maintenance durvalumab and bevacizumab plus olaparib (arm 3).1

Platinum-based chemotherapy was administered every 3 weeks for up to 6 cycles, and bevacizumab was administered every 3 weeks for up to 15 months. Durvalumab or placebo was given every 3 weeks for up to 24 months, and olaparib or placebo was administered twice daily for up to 24 months.

The trial’s primary end point was investigator-assessed PFS for arm 3 vs arm 1 in the overall trial population, including patients without BRCA mutations, and in the subset of these patients with homologous recombination–deficient disease. Key secondary end points consisted of investigator-assessed PFS in arm 2 vs arm 1, and OS.

More than 1200 patients were enrolled in DUO-O across all treatment arms at 179 study locations.

Regarding toxicity, the safety and tolerability findings for these combinations were consistent with data observed in prior clinical trials and the known profiles of the individual agents.

“While there has been significant progress for patients with advanced ovarian cancer, an unmet need still remains. These data from the DUO-O trial provide encouraging evidence for this [olaparib] and [durvalumab] combination in patients without tumor BRCA mutations and reinforce our continued commitment to finding new treatment approaches for these patients,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, stated in a news release. “It will be important to understand the key secondary end points as well as data for relevant subgroups.”

References

1. Lynparza and Imfinzi combination improved progression-free survival in newly diagnosed patients with advanced ovarian cancer without tumour BRCA mutations in DUO-O phase III trial. News release. AstraZeneca. April 5, 2023. Accessed April 5, 2023. https://www.astrazeneca.com/media-centre/press-releases/2023/
2. Durvalumab treatment in combination with chemotherapy and bevacizumab, followed by maintenance durvalumab, bevacizumab and olaparib treatment in advanced ovarian cancer patients (DUO-O). ClinicalTrials.gov. Updated February 21, 2023. Accessed April 5, 2023. https://clinicaltrials.gov/ct2/show/NCT03737643