Quintuple Regimen Prolongs PFS in Advanced, High-Grade Epithelial Ovarian Cancer +/- BRCA Mutations

Philipp Harter, MD, PhD

Treatment with olaparib (Lynparza), durvalumab (Imfinzi), chemotherapy, and bevacizumab (Avastin) extended progression-free survival (PFS) in patients with newly-diagnosed, advanced, high-grade epithelial ovarian cancer with or without BRCA mutations.¹

The PFS result, which comes from the phase 3 DUO-O study (NCT03737643), was statistically significant and clinically meaningful. Moreover, findings from an additional arm in which patients were administered durvalumab, chemotherapy, and bevacizumab, showed a numerical PFS improvement, but the result was not statistically significant.

Olaparib, durvalumab, chemotherapy, and bevacizumab combined showed consistent safety and tolerability compared with prior clinical trials and the known profiles of each drug. Data from the study will be presented at upcoming medical meeting 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. 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," said Philipp Harter, MD, PhD, director, Department of Gynecology and Gynecologic Oncology, Evangelische Kliniken Essen-Mitte, and principal investigator of DUO-O, in a press release.

In the 2-cohort, double-blind study, patients with newly diagnosed, advanced, ovarian cancer who were 18 years of age or older (20 years or older in Japan) with an ECOG performance status of 0-1 and preserved organ and bone marrow function were included. Patients must have been candidates for cytoreductive surgery, have had evidence of the presence or absence of BRCA 1/2 mutations in tumor tissue, available tumor sample for centralized BRCA testing, and be postmenopausal.²

Over 1200 patients from 179 locations around the world were randomized 1:1:1 in the study.¹

The study evaluated the comparator combination across 3 treatment arms. Patients in arm 1 received platinum-based chemotherapy consisting of carboplatin and paclitaxel in combination with bevacizumab and durvalumab placebo followed by maintenance bevacizumab, durvalumab placebo, and olaparib. In arm 2, patients were given carboplatin/paclitaxel in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab, and olaparib placebo.²

Patients in arm 3 received carboplatin/paclitaxel in combination with bevacizumab and durvalumab followed by maintenance bevacizumab, durvalumab, and olaparib. Bevacizumab treatment in this arm was optional and varied according to local practice. Finally, in the BRCA-mutant (BRCAm) cohort, patients were administered carboplatin/paclitaxel combined with bevacizumab and durvalumab, followed by maintenance bevacizumab, durvalumab and olaparib. Bevacizumab was also optional for this group.

In approximately 1374 patients, investigators assessed the coprimary end points of PFS and PFS in the non-BRCAm population. The secondary end points explored in the non-BRCAm population included PFS, overall survival, second progression (PFS2), health-related quality-of-life (HRQL), pathological complete response (pCR), pharmacokinetics, objective response rate (ORR), duration of response, time to first subsequent therapy (TFST), time to second subsequent therapy (TSST), and time to treatment discontinuation (TDT). In the BRCAm patients, investigators also evaluated PFS, PFS2, ORR, SOR, TFST, TSST, TDT, HRQOL, and pCR.

“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 Lynparza and Imfinzi combination in patients without tumor BRCA mutations and reinforce our continued commitment to finding new treatment approaches for these patients. It will be important to understand the key secondary endpoints as well as data for relevant subgroups,” said Susan Galbraith, executive vice president, oncology research and development, AstraZeneca, in the press release.

_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/lynparza-imfinzi-met-endpoint-in-ovarian-cancer.html}

_{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}