Lynparza + Imfinzi combination reduced risk of disease progression or death by 37% vs. chemotherapy and bevacizumab in advanced ovarian cancer without tumour BRCA mutations in the DUO-O Phase III trial -AstraZenecA

Patients were treated with Imfinzi in combination with chemotherapy and bevacizumab followed by Imfinzi, Lynparza and bevacizumab as maintenance therapy. These results were presented in an oral presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract #LBA5506).

The combination of Lynparza, Imfinzi, chemotherapy and bevacizumab reduced the relative risk of disease progression or death by 37% versus chemotherapy and bevacizumab (hazard ratio (HR) 0.63; 95% CI 0.52-0.76; p<0.0001). median pfs was 24.2 months versus 19.3, respectively. in the homologous recombination deficiency (hrd)-positive subgroup of patients, lynparza, imfinzi, chemotherapy and bevacizumab reduced the relative risk of disease progression or death by 51% versus chemotherapy and bevacizumab alone (hr 0.49; 95% ci 0.34-0.69; p><0.0001). median pfs was 37.3 months versus 23.0, respectively.></0.0001).></0.0001).>

Professor Philipp Harter, Director, Department of Gynaecology and Gynaecologic Oncology, Evangelische Kliniken Essen-Mitte, Germany, and principal investigator for the trial, said: “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 tumour BRCA mutations.”

At a pre-planned exploratory analysis of the HRD-negative subgroup of patients , Lynparza, Imfinzi, chemotherapy and bevacizumab reduced the relative risk of disease progression or death by 32% versus chemotherapy and bevacizumab (HR 0.68; 95% CI 0.54-0.86). Median PFS was 20.9 months versus 17.4. At the time of this interim analysis, an additional arm evaluating the combination of Imfinzi, chemotherapy and bevacizumab demonstrated a numerical improvement in PFS which was not statistically significant (HR 0.87; 95% CI 0.73-1.04; p=0.13). At the time of this planned interim analysis, the overall survival (OS) and other secondary endpoints were immature. OS will be formally assessed at a subsequent analysis.

The safety and tolerability of these combinations was broadly consistent with that observed in prior clinical trials and the known profiles of the individual medicines. The most common adverse events (AEs) (greater than or equal to 20% of patients) for the combination of Lynparza, Imfinzi, chemotherapy and bevacizumab were nausea (57%), anaemia (55%), neutropenia (51%), fatigue/asthenia (49%), arthralgia (34%), constipation (30%), diarrhoea (30%), thrombocytopenia (28%), hypertension (26%), vomiting (26%), leukopenia (24%), headache (22%), abdominal pain (21%) and hypothyroidism (20%). Grade 3 or higher AEs were neutropenia (31%), anaemia (24%), leukopenia (8%), hypertension (7%) and thrombocytopenia (6%).

Approximately 65% of patients treated with the combination of Lynparza, Imfinzi, chemotherapy and bevacizumab who experienced AEs during chemotherapy and throughout the maintenance phase remained on treatment at the time of data cut-off, compared to 80% of patients in the control arm (chemotherapy plus bevacizumab).