Oyama Masafumi, Sugiyama Takayuki, Nozawa Masahiro, Fujimoto Kiyohide, Kishida Takeshi, Kimura Go, Tokuda Noriaki, Hinotsu Shiro, Shimozuma Kojiro, Akaza Hideyuki, Ozono Seiichiro
Saitama Medical University International Medical Center, Hidaka, Japan.
Hamamatsu University School of Medicine, Hamamatsu, Japan.
Jpn J Clin Oncol. 2017 Jun 1;47(6):551-559. doi: 10.1093/jjco/hyw194.
Many studies have shown the efficacy of everolimus after pretreatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors. We investigated the efficacy and safety of everolimus as a second-line treatment after the failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy in Japanese patients with advanced renal cell carcinoma.
This was an open-label, multicenter, phase II trial conducted in Japan through the central registration system. A total of 57 patients were enrolled. Patients were administered 10 mg of everolimus q.d. orally. The primary efficacy endpoint was progression-free survival achieved by administration of everolimus.
The median progression-free survival of patients administered everolimus was 5.03 months (95% confidence interval: 3.70-6.20). The median overall survival was not reached. The objective response rate was 9.4% (95% confidence interval: 3.1-20.7). The progression-free survival in the group of <100% relative dose intensity was 6.70 months (95% confidence interval: 4.13-11.60), and that in the group of 100% relative dose intensity was 3.77 months (hazard ratio: 2.79, 95% confidence interval: 2.77-5.63). The commonly observed adverse events and laboratory abnormalities were stomatitis (49.1%), hypertriglyceridemia (26.4%), interstitial lung disease (26.4%), anemia (22.6%) and hypercholesterolemia (22.6%).
The median progression-free survival was almost similar to that recorded in the RECORD-1 study, whereas prolongation of overall survival was observed in the present study compared with the RECORD-1 study. The treatment outcomes of first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy and second-line everolimus treatment in Japanese patients were successfully established in the present study.
许多研究已显示依维莫司在经血管内皮生长因子受体-酪氨酸激酶抑制剂预处理后的疗效。我们调查了依维莫司作为日本晚期肾细胞癌患者血管内皮生长因子受体-酪氨酸激酶抑制剂治疗失败后的二线治疗的疗效和安全性。
这是一项通过中央注册系统在日本进行的开放标签、多中心、II期试验。共纳入57例患者。患者口服依维莫司10mg，每日一次。主要疗效终点是依维莫司给药后实现的无进展生存期。
接受依维莫司治疗的患者的中位无进展生存期为5.03个月（95%置信区间：3.70-6.20）。中位总生存期未达到。客观缓解率为9.4%（95%置信区间：3.1-20.7）。相对剂量强度<100%组的无进展生存期为6.70个月（95%置信区间：4.13-11.60），相对剂量强度为100%组的无进展生存期为3.77个月（风险比：2.79，95%置信区间：2.77-5.63）。常见的不良事件和实验室异常包括口腔炎（49.1%）、高甘油三酯血症（26.4%）、间质性肺病（26.4%）、贫血（22.6%）和高胆固醇血症（22.6%）。
中位无进展生存期与RECORD-1研究记录的相近，而与RECORD-1研究相比，本研究观察到总生存期有所延长。本研究成功确立了日本患者一线血管内皮生长因子受体-酪氨酸激酶抑制剂治疗和二线依维莫司治疗的治疗结果。
