沃利替尼联合依维莫司治疗转移性肾细胞癌的疗效和安全性：一项三臂、随机、双盲、多中心 III 期研究（CONCEPT）。
Efficacy and safety of vorolanib plus everolimus in metastatic renal cell carcinoma: A three-arm, randomised, double-blind, multicentre phase III study (CONCEPT).
机构信息
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
出版信息
Eur J Cancer. 2023 Jan;178:205-215. doi: 10.1016/j.ejca.2022.10.025. Epub 2022 Nov 1.
BACKGROUND
Vorolanib is a highly potent tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor. This three-arm, randomised, registered study aimed to assess the combination of vorolanib and everolimus or vorolanib alone versus a control arm of everolimus as second-line treatment in patients with metastatic renal cell carcinoma (RCC).
PATIENTS AND METHODS
Patients with advanced or metastatic RCC who had received one prior VEGFR-TKI were randomised (1:1:1) to receive the combination of vorolanib and everolimus or either monotherapy. Patients with brain metastases were excluded. The primary end-point was progression-free survival (PFS) assessed by the independent review committee per Response Evaluation Criteria in Solid Tumours v1.1.
RESULTS
Between 10th March 2017 and 30th May 2019, 399 patients (133 in each group) were enrolled. By the cutoff date (30th April 2020), a significant improvement in PFS was detected in the combination group compared with the everolimus group (10.0 versus 6.4 months; hazard ratio, 0.70; P = 0.0171). PFS was similar between the vorolanib group and the everolimus group (median: 6.4 versus 6.4 months; hazard ratio, 0.94; P = 0.6856). A significantly higher objective response rate was observed in the combination group than in the everolimus group (24.8% versus 8.3%; P = 0.0003), whereas there was no significant difference between the vorolanib group and the everolimus group (10.5% versus 8.3%; P = 0.5278). The overall survival data were immature. A total of 96 (72.2%), 52 (39.1%) and 71 (53.4%) grade 3 or higher treatment-related adverse events occurred in the combination group, vorolanib group and everolimus group, respectively.
CONCLUSIONS
The addition of vorolanib to everolimus as 2nd-line treatment for patients with advanced or metastatic RCC who have experienced cancer progression after VEGFR-TKI therapy provided a better objective response rate and PFS than everolimus alone with a manageable safety profile.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03095040; Chinadrugtrials, CTR20160987.
背景
Vorolanib 是一种高效的酪氨酸激酶抑制剂（TKI），靶向血管内皮生长因子受体（VEGFR）和血小板衍生生长因子受体。这项三臂、随机、注册研究旨在评估 Vorolanib 联合 Everolimus 或单独使用 Vorolanib 与 Everolimus 作为二线治疗转移性肾细胞癌（RCC）患者的疗效。
方法
接受过一种血管内皮生长因子受体酪氨酸激酶抑制剂（VEGFR-TKI）治疗的晚期或转移性 RCC 患者按 1:1:1 随机分配至接受 Vorolanib 联合 Everolimus 或单独接受单药治疗。排除有脑转移的患者。主要终点是独立评审委员会按照实体瘤反应评价标准 1.1 评估的无进展生存期（PFS）。
结果
2017 年 3 月 10 日至 2019 年 5 月 30 日期间，共纳入 399 例患者（每组 133 例）。截至截止日期（2020 年 4 月 30 日），与 Everolimus 组相比，联合组的 PFS 显著改善（10.0 个月比 6.4 个月；风险比，0.70；P=0.0171）。Vorolanib 组与 Everolimus 组的 PFS 相似（中位数：6.4 个月比 6.4 个月；风险比，0.94；P=0.6856）。联合组的客观缓解率显著高于 Everolimus 组（24.8%比 8.3%；P=0.0003），而 Vorolanib 组与 Everolimus 组之间无显著差异（10.5%比 8.3%；P=0.5278）。总生存数据不成熟。联合组、Vorolanib 组和 Everolimus 组分别有 96（72.2%）、52（39.1%）和 71（53.4%）例患者发生 3 级或更高级别的治疗相关不良事件。
结论
在接受过 VEGFR-TKI 治疗后出现癌症进展的晚期或转移性 RCC 患者中，Vorolanib 联合 Everolimus 作为二线治疗可提高客观缓解率和 PFS，且安全性可管理。
试验注册
ClinicalTrials.gov，NCT03095040；中国临床试验注册中心， CTR20160987。
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