Durvalumab Combo Shows Sustained PFS Benefit in Advanced Ovarian Cancer
核心洞察
Durvalumab plus chemotherapy and bevacizumab, followed by maintenance with olaparib, durvalumab, and bevacizumab, significantly improved progression-free survival (PFS).
In patients with BRCA (搜索)-unmutated, HRD-positive ovarian cancer (搜索), median PFS was 45.1 months in the treatment arm versus 23.3 months in the control arm.
In the BRCA (搜索)-unmutated ITT population, median PFS was 25.1 months for the durvalumab combination arm compared to 19.3 months for the control arm.
Updated results from the phase 3 DUO-O trial demonstrate that durvalumab (Imfinzi) in combination with chemotherapy and bevacizumab (Avastin), followed by maintenance with olaparib (Lynparza), durvalumab, and bevacizumab, continues to show a clinically meaningful progression-free survival (PFS) benefit in patients with newly diagnosed advanced ovarian cancer (搜索) who do not harbor BRCA1/2 mutations. The findings, presented at the 2024 European Society for Medical Oncology Gynaecological Cancers Congress, highlight the potential of this combination as a first-line treatment option.
In the BRCA (搜索)-unmutated, homologous recombination deficient (HRD)–positive subgroup, the median PFS was 45.1 months in the treatment arm (n = 140) compared with 23.3 months in the control arm (n = 143), resulting in a hazard ratio (HR) of 0.46 (95% CI, 0.33-0.65). Patients treated with durvalumab plus chemotherapy and bevacizumab, followed by maintenance durvalumab plus bevacizumab (n = 148), achieved a median PFS of 25.1 months (HR vs control arm, 0.89; 95% CI, 0.67-1.19).
PFS Benefit in ITT Population
In the BRCA (搜索)-unmutated, intention-to-treat (ITT) population, the median PFS was 25.1 months for the durvalumab combination arm (n = 578) versus 19.3 months for the control arm (n = 378), with a hazard ratio of 0.61 (95% CI, 0.51-0.73). The median PFS for the arm receiving durvalumab plus chemotherapy and bevacizumab, followed by durvalumab plus bevacizumab, was 20.6 months (HR vs control arm, 0.87; 95% CI, 0.74-1.03; P = .11).
Expert Commentary
"DUO-O continues to demonstrate a clinically meaningful PFS benefit with first-line durvalumab, chemotherapy, and bevacizumab, followed by durvalumab, bevacizumab, and olaparib maintenance versus the control," said Dr. Fabian Trillsch, deputy director of Polyclinic for Gynecology and Obstetrics at Ludwig-Maximilians-University of Munich Hospital (搜索) in Germany.
Previous Findings
An earlier interim PFS analysis presented at the 2023 American Society of Clinical Oncology Annual Meeting also demonstrated a statistically significant improvement in PFS with the investigational approach compared to the control arm.
In patients with HRD-positive disease, the median PFS was 37.3 months in the durvalumab combination arm compared with 23.0 months in the control arm (HR, 0.49; 95% CI, 0.34-0.69; P < .0001). In the ITT population, the median PFS was 24.2 months in the durvalumab combination arm versus 19.3 months in the control arm (HR, 0.63; 95% CI, 0.52-0.76; P < .0001).
Study Design
The DUO-O trial enrolled patients with newly diagnosed, FIGO stage III to IV high-grade epithelial ovarian cancer (搜索) who did not harbor BRCA (搜索) mutations, were treatment-naive, and had undergone primary debulking or planned interval debulking surgery. Patients received carboplatin plus paclitaxel during cycle 1 before being randomized 1:1:1. After the chemotherapy phase, patients with a response, stable disease, or no evidence of disease were allowed to receive maintenance therapy.
In the control arm, patients received carboplatin and paclitaxel plus bevacizumab prior to maintenance bevacizumab. The second arm received durvalumab plus carboplatin, paclitaxel, and bevacizumab, followed by bevacizumab and durvalumab in the maintenance phase. The third arm received durvalumab plus carboplatin, paclitaxel, and bevacizumab, followed by maintenance bevacizumab, durvalumab, and olaparib.
The primary endpoint of the study was PFS per RECIST 1.1 criteria for the durvalumab combination arm versus the control arm in the HRD-positive and ITT populations. Key secondary endpoints included overall survival (OS), PFS2, and safety.
Overall Survival and PFS2
In the HRD-positive cohort, the median OS was not reached in all three arms; however, trends favored the durvalumab combination arm versus the control arm (HR, 0.84; 95% CI, 0.51-1.37; P = .48) and the arm receiving durvalumab plus chemotherapy and bevacizumab followed by durvalumab plus bevacizumab versus the control arm (HR, 0.69; 95% CI, 0.41-1.15). In the ITT population, the median OS was 48.5 months in the durvalumab combination arm versus 48.0 months in the control arm (HR, 0.95; 95% CI, 0.76-1.20; P = 0.68).
In the HRD-positive cohort, the median PFS2 was not reached for the durvalumab combination arm versus 42.0 months for the control arm (HR, 0.62; 95% CI, 0.40-0.95). In the ITT cohort, the median PFS2 was 35.4 months in the durvalumab combination arm versus 32.8 months in the control arm (HR, 0.82; 95% CI, 0.67-1.01).
Safety Profile
Safety findings were consistent with the primary analysis of the study. The most common grade 3 or higher adverse events in the durvalumab combination arm were neutropenia (31%) and anemia (25%).
Conclusion
"DUO-O is ongoing, and further insight into the long-term benefit of the combination will be provided with additional follow-up," concluded Dr. Trillsch.