Results from an interim analysis of the Phase III DUO-O trial, presented at the 2023 ASCO Annual Meeting, revealed that the combination of LYNPARZA, IMFINZI, chemotherapy, and bevacizumab demonstrated a significant 37% reduction in the risk of disease progression or death compared to chemotherapy and bevacizumab alone. The median progression-free survival (PFS) was 24.2 months in the combination group and 19.3 months in the control group. In the subgroup of patients with homologous recombination deficiency (HRD) positivity, the combination therapy resulted in an even greater 51% reduction in the risk of disease progression or death, with a median PFS of 37.3 months compared to 23.0 months in the control group.
The late-stage study, dubbed DUO-O, evaluated IMFINZI (durvalumab), in combination with platinum-based chemotherapy and Roche's AVASTIN (bevacizumab) followed by maintenance treatment with IMFINZI and bevacizumab with or without LYNPARZA (olaparib) in newly diagnosed patients with advanced high-grade epithelial ovarian cancer without tumor BRCA mutations.
During a pre-planned exploratory analysis focusing on the HRD-negative subgroup of patients, the combination of LYNPARZA, IMFINZI, chemotherapy, and bevacizumab showed a 32% reduction in the relative risk of disease progression or death compared to chemotherapy and bevacizumab alone. The median PFS was 20.9 months versus 17.4 months. At the time of this interim analysis, an additional treatment arm investigating the combination of IMFINZI, chemotherapy, and bevacizumab demonstrated a slight improvement in PFS, although the improvement did not reach statistical significance.
At the scheduled interim analysis, the evaluation of overall survival (OS) and other secondary endpoints was still ongoing and not yet fully mature. The formal assessment of OS will be conducted in a subsequent analysis.
The most commonly reported adverse events (AEs) occurring in 20% or more of patients who received the combination of LYNPARZA, IMFINZI, chemotherapy, and bevacizumab were nausea (57%), anemia (55%), neutropenia (51%), fatigue/asthenia (49%), arthralgia (34%), constipation (30%), diarrhea (30%), thrombocytopenia (28%), hypertension (26%), vomiting (26%), leukopenia (24%), headache (22%), abdominal pain (21%), and hypothyroidism (20%). Grade 3 or higher AEs included neutropenia (31%), anemia (24%), leukopenia (8%), hypertension (7%), and thrombocytopenia (6%).
Among patients who received the combination of LYNPARZA, IMFINZI, chemotherapy, and bevacizumab and encountered adverse events (AEs) during chemotherapy and the maintenance phase, around 65% continued their treatment at the time of data analysis. In comparison, 80% of patients in the control arm (chemotherapy plus bevacizumab) remained on treatment.
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KOL insights
“DUO-O showcases the power of academia and industry collaboration in advancing new treatment combinations for patients with ovarian cancer” –Expert Opinion.
“The primary aim of first-line treatment of patients with advanced ovarian cancer is long-term control over the disease, but still too many patients progress quickly and face poor clinical outcomes today. Data from the DUO-O trial interim progression-free survival analysis provide evidence for further improvement with olaparib and durvalumab combination versus chemotherapy and bevacizumab alone in patients without tumor BRCA mutations”–Expert Opinion.
“Interesting study looking at addition of durvalumab and olaparib to chemo+bev in upfront/maintenance treatment of advanced ovarian cancer. PFS results are compelling but we need Arm 2 comparison data to see if the PFS benefit is explained by olaparib alone”- Expert Opinion.
Conclusion
In the treatment of newly diagnosed ovarian cancer without a BRCA1/2 mutation, combining frontline chemotherapy with AVASTIN and IMFINZI, followed by maintenance treatment with bevacizumab plus durvalumab and LYNPARZA, showed a statistically significant and clinically meaningful improvement in PFS compared to maintenance bevacizumab alone. The safety profile of the treatment was generally consistent with what is already known about each agent. The trial is still ongoing to further evaluate PFS, OS, and other important secondary endpoints.
AstraZeneca's IMFINZI has shown promising results in ovarian cancer, which has been a challenging area for anti-PD-(L) drugs. This outcome is particularly noteworthy because it appears to have succeeded where other combinations of PD-(L)1 inhibitors and PARP inhibitors have failed. One possible reason for this success could be AstraZeneca's deliberate exclusion of BRCA-positive patients, who typically respond well to AVASTIN/LYNPARZA treatment alone.
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