Ostrowska-Leśko Marta, Mądry Radosław, Bobiński Marcin
Independent Laboratory of Translational Medicine, Chair of Medical Genetics, Medical University of Lublin, Lublin, Poland.
Klinika Ginekologii Onkologicznej, Uniwersytet Medyczny w Poznaniu, Poznan, Poland.
Trials. 2025 Sep 1;26(1):325. doi: 10.1186/s13063-025-09062-8.
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.
随着贝伐单抗纳入标准治疗方案，晚期卵巢癌的管理有了显著进展。虽然贝伐单抗的疗效已在如GOG218、ICON7和PAOLA-1等试验中得到证实，但对于7.5mg/kg剂量相对于15mg/kg方案的优势，仍存在认识上的差距。本研究通过评估这两种给药策略的疗效、安全性和成本效益来填补这一差距，同时考虑患者特征的异质性，包括BRCA突变状态和同源重组缺陷（HRD）。这项多中心、随机临床试验将招募新诊断的晚期（FIGO III/IV期）卵巢癌、输卵管癌或原发性腹膜癌患者。参与者将接受三个周期的含贝伐单抗新辅助化疗，随后进行间隔减瘤手术，并根据BRCA和HRD状态随机分为四个治疗组。患者在辅助治疗阶段将接受7.5mg/kg或15mg/kg贝伐单抗联合化疗，并持续进行长达64周的维持治疗，可加用或不加用奥拉帕利。主要终点是无进展生存期。次要终点包括总缓解率、生活质量和安全性。数据分析重点在于对BRCA和HRD状态对治疗结果影响的亚组评估。本研究有望为优化贝伐单抗给药提供关键见解，可能使在不影响疗效的情况下纳入具有成本效益和更安全的治疗方案成为可能。试验注册号：EUCT编号：2023 - 509659 - 15 - 00。于2024年7月9日注册。
