Abstract
The management of advanced ovarian cancer has significantly developed with the integration of bevacizumab into standard therapeutic regimens. While the efficacy of bevacizumab has been established in trials such as GOG218, ICON7, and PAOLA-1, there remains a gap in understanding the advantages of the 7.5 mg/kg dose over the 15 mg/kg regimen. This study addresses this gap by evaluating the efficacy, safety, and cost effectiveness of these two dosing strategies, considering the heterogeneity of patient profiles, including BRCA mutation status and homologous recombination deficiency (HRD). This multicenter, randomized clinical trial will recruit patients with newly diagnosed, advanced-stage (FIGO III/IV) ovarian, fallopian tube, or primary peritoneal cancer. Participants will undergo three cycles of neoadjuvant chemotherapy with bevacizumab, followed by interval debulking surgery and randomization into four treatment arms stratified by BRCA and HRD status. Patients will receive either 7.5 mg/kg or 15 mg/kg bevacizumab in combination with chemotherapy during the adjuvant treatment phase and continue with maintenance therapy for up to 64 weeks, with or without the addition of olaparib. The primary endpoint is progression-free survival. The secondary endpoints include the overall response rate, quality of life, and safety profile. Data analysis focuses on subgroup evaluation of the influence of BRCA and HRD status on treatment outcomes. This study is expected to provide critical insights into optimizing bevacizumab dosing, potentially enabling the inclusion of cost-effective and safer treatment protocols without compromising efficacy. TRIAL REGISTRATION: EUCT number: 2023-509659-15-00. Registered on 09.07.2024.