In the randomized phase II REGOMA trial, regorafenib showed promising activity in patients with recurrent glioblastoma. We conducted a large, multicenter, prospective, observational study to confirm the REGOMA data in a real-world setting. The major inclusion criteria were histologically confirmed diagnosis of glioblastoma according to the World Health Organization (WHO) 2016 classification and relapse after radiotherapy with concurrent/adjuvant temozolomide treatment, good performance status [Eastern Cooperative Oncology Group performance status (ECOG PS 0-1)] and good liver function. Regorafenib was administered at the standard dose of 160 mg/day for 3 weeks on/1 week off. Brain magnetic resonance imaging was carried out within 14 days before starting regorafenib and every 8-12 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate, disease control rate (DCR), safety and health-related quality of life. The Response Assessment in Neuro-Oncology (RANO) criteria were used for response evaluation and Common Terminology Criteria for Adverse Events (CTCAE) version 5 for assessment of adverse events (AEs). From September 2020 to October 2022, 190 patients with recurrent glioblastoma were enrolled from 30 cancer centers in Italy: their median age was 58.5 years [interquartile range (IQR) 53-67 years], 68% were male and 85 (44.7%) were in optimal clinical condition (ECOG PS 0). The number of patients taking steroids at baseline was 113 (60%); the second surgery was carried out in 39 (20.5%). O-methylguanine-DNA methyltransferase (MGMT) was methylated in 80 patients (50.3%) and 147 (92.4%) of the patients analyzed had isocitrate dehydrogenase (IDH) wild type. The median follow-up period was 20 months (IQR 15.6-25.5 months). The median OS was 7.9 months ([95% confidence interval (CI) 6.5-9.2 months] and the median PFS was 2.6 months (95% CI 2.3-2.9 months). Radiological response was partial response and stable disease in 13 (7.3%) and 26 (14.6%) patients, respectively, with a DCR of 21.9%. The median number of regorafenib cycles per patient was 3 (IQR 2.0-4.0). Grade 3-4 drug-related adverse events were reported in 22.6% of patients. A dose reduction due to AEs was required in 36% of patients. No deaths were considered as treatment-related AEs. This large, real-world observational study showed similar OS with better tolerability of regorafenib in patients with relapsed glioblastoma compared with the REGOMA study.

中文翻译：

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REGOMA-OSS：一项大型、意大利、多中心、前瞻性、观察性研究，评估瑞戈非尼对复发性胶质母细胞瘤患者的疗效和安全性

在随机 II 期 REGOMA 试验中，瑞格非尼在复发性胶质母细胞瘤患者中显示出有希望的活性。我们进行了一项大型、多中心、前瞻性观察研究，以在现实环境中确认 REGOMA 数据。主要纳入标准是根据世界卫生组织 (WHO) 2016 年分类，组织学确诊为胶质母细胞瘤，并在同步/辅助替莫唑胺治疗的放疗后复发，体能状态良好[东部肿瘤合作组体能状态 (ECOG PS 0-1)]和良好的肝功能。瑞戈非尼以 160 mg/天的标准剂量给药，持续 3 周/停药 1 周。在开始使用瑞戈非尼之前 14 天内进行一次脑磁共振成像，每 8-12 周进行一次。主要终点是总生存期（OS）。次要终点是无进展生存期（PFS）、客观缓解率、疾病控制率（DCR）、安全性和健康相关的生活质量。神经肿瘤学反应评估 (RANO) 标准用于反应评估，不良事件通用术语标准 (CTCAE) 版本 5 用于评估不良事件 (AE)。 2020年9月至2022年10月，来自意大利30个癌症中心的190名复发性胶质母细胞瘤患者入组：他们的中位年龄为58.5岁[四分位距（IQR）53-67岁]，68%为男性，85名（44.7%）为女性处于最佳临床状态 (ECOG PS 0)。基线时服用类固醇的患者人数为 113 人（60%）； 39 例（20.5%）进行了第二次手术。 80 名患者 (50.3%) 的 O-甲基鸟嘌呤-DNA 甲基转移酶 (MGMT) 被甲基化，其中 147 名 (92.4%) 的分析患者具有异柠檬酸脱氢酶 (IDH) 野生型。中位随访期为 20 个月（IQR 15.6-25.5 个月）。中位 OS 为 7.9 个月（[95% 置信区间 (CI) 6.5-9.2 个月]，中位 PFS 为 2.6 个月（95% CI 2.3-2.9 个月）。放射学反应为部分缓解和疾病稳定，13 例（7.3%） ）和 26 名患者（14.6%），DCR 为 21.9%。每位患者的瑞戈非尼周期中位数为 3 个（IQR 2.0-4.0）。22.6% 的患者报告了 3-4 级药物相关不良事件。 36% 的患者因 AE 需要减少剂量。没有死亡被视为与治疗相关的 AE。这项大型、真实世界的观察性研究显示，与复发性胶质母细胞瘤患者相比，瑞戈非尼在复发性胶质母细胞瘤患者中具有相似的 OS 和更好的耐受性。雷戈玛研究。