Imfinzi Combo Improves Progression Free Survival in Ovarian Cancer

Platinum-based chemotherapy plus Imfinzi (durvalumab), Avastin (bevacizumab), and Lynparza (olaparib) showed a statistically significant and clinically meaningful improvement in median progression-free survival versus chemotherapy and Avastin for the treatment of patients with newly diagnosed non-tBRCA–mutated ovarian cancer, but did not provide a significant overall survival benefit, according to final overall survival data from the DUO-O trial presented during the 2025 ESMO Congress.

At a median follow-up of 56 months, findings from the third data cutoff demonstrated that the median progression-free survival among patients with non-tBRCA–mutated disease in the intention-to-treat population who received chemotherapy with Imfinzi, Avastin, and Lynparza (arm 3; 378 patients) was 25.1 months compared with 19.3 months among those who received chemotherapy and Avastin (arm 1; 378 patients). Patients who received chemotherapy plus Avastin and Imfinzi (arm 2; 374 patients) had a median progression-free survival of 20.6 months, representing a benefit versus arm 1.

The 24- and 48-month progression-free survival rates were 53% and 30% in arm 3; these respective rates were 39% and 22% in arm 2 and 33% and 16% in arm 1. However, the median overall survival in arm 3 was 50.5 months compared with 49.6 months in arm 1. Similarly, the median overall survival in arm 2 was 48.5 months, which did not represent a significant benefit versus arm 1. In arm 3, the 24- and 48-month overall survival rates were 83% and 53%; these respective rates were 81% and 51% in arm 2 and 80% and 51% in arm 1.

“DUO-O met both primary end points at data cutoff 1, with a statistically significant and clinically meaningful progression-free survival improvement for arm 3 versus arm 1 in the HRD-positive and intention-to-treat populations; this benefit was maintained at data cutoff 3 with an approximate median follow-up of 56 months,” Dr. Carol Aghajanian, the chief of the Gynecologic Medical Oncology Service and the Avon Chair in Gynecologic Oncology Research at Memorial Sloan Kettering Cancer Center in New York, New York, said during the presentation. “At this final overall survival analysis, the observed progression-free survival benefits did not translate into a statistically significant overall survival improvement.”

What was the Study Design of DUO-O?

DUO-O was a double-blind, multicenter study that examined Imfinzi plus platinum-based chemotherapy and Avastin followed by maintenance Imfinzi and Avastin or Imfinzi, Avastin, and Lynparza in patients with newly diagnosed advanced ovarian cancer. Eligible patients needed to have FIGO stage 3 to 4 ovarian, primary peritoneal, and/or fallopian-tube cancer, as well as be candidates for cytoreductive surgery. Patients also needed to be at least 18 years old, or at least 20 years old if they enrolled in Japan, have an ECOG performance status of 0 or 1, and have preserved organ and bone marrow function. Eligible patients were randomly assigned one-to-one-to-one to arms 1, 2, or 3.

During the chemotherapy phase, all patients received chemotherapy in combination with Avastin; those in arms 2 and 3 also received Imfinzi. During the maintenance phase, patients in arms 1, 2, and 3 received Avastin, Avastin plus Imfinzi, or Avastin plus Imfinzi and Lynparza, respectively. Maintenance therapy continued for up to 2 years. The primary end point was investigator-assessed progression-free survival per RECIST 1.1 criteria in arm 3 versus arm 1 in both the non-BRCA–mutated HRD-positive and intention-to-treat populations. Key secondary end points included investigator-assessed progression-free survival per RECIST 1.1 criteria in arm 2 versus arm 1 in the non-BRCA–mutated intention-to-treat population, overall survival, and safety.

Additional Efficacy and Safety Results

Additional efficacy findings from DUO-O data cutoff 3 revealed that the median progression-free survival among patients with non-tBRCA–mutated, HRD-positive disease was 45.1 months in arm 3 (140 patients) compared with 23.3 months in arm 1 (143 patients). In arm 2 (148 patients), the median progression-free survival was 25.6 months, representing a benefit versus arm 1. In arm 3, the 24- and 48-month progression-free survival rates were 73% and 47%; these respective rates were 52% and 31% in arm 2 and 47% and 27% in arm 1.

In terms of overall survival among patients with non-tBRCA–mutated, HRD-positive disease, the median value was not reached in arms 2 and 3. When compared with the 66.8-month median overall survival in arm 1, patients in arm 3 experienced a 20% reduction in the risk of death and those in arm 2 had a 16% reduction. In arm 3, the 24- and 48-month overall survival rates were 96% and 71%; these respective rates were 92% and 71% in arm 2 and 89% and 68% in arm 1.

In terms of safety, any-grade side effects were reported in arms 1 (99.2%), 2 (99.5%), and 3 (99.2%). Grade 3 (severe) or higher side effects (62% versus 66% versus 73%), side effects leading to death (1.3% versus 2.4% versus 2.1%), serious side effects (35% versus 44% versus 40%), immune-mediated side effects (35% versus 57% versus 54%), side effects leading to dose modification (72% versus 80% versus 86%), and side effects leading to treatment discontinuation (21% versus 27% versus 35%) were reported in all three arms. Side effects of special interest associated with Lynparza that occurred in all three arms consisted of new primary malignancies (0.8% versus 0.3% versus 1.9%) and pneumonitis (0.8% versus 1.6% versus 1.9%).

“Safety continues to be generally consistent with the known profiles of each agent,” Aghajanian said in her conclusion.

References

1. “Imfinzi + paclitaxel/carboplatin + Avastin followed by Imfinzi, Avastin + Lynparza maintenance in patients with newly diagnosed non-tBRCA–mutated advanced ovarian cancer: final overall survival from DUO-O” by Dr. Carol Aghajanian, et al., Presented at the 2025 ESMO Congress
2. “Imfinzi treatment in combination with chemotherapy and Avastin, followed by maintenance Imfinzi, Avastin, and Lynparza in advanced ovarian cancer patients (DUO-O)” by Dr. Carol Aghajanian, ClinicalTrials.gov

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.