Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab
Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab
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DOI：
10.1200/jco.2014.58.1041
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发表时间：
2015-06-20
影响因子：
45.3
通讯作者：
Atkins, Michael B.
中科院分区：
文献类型：
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作者：
McDermott, David F.;Drake, Charles G.;Atkins, Michael B.
目的 使用全人源免疫球蛋白G4抗体纳武利尤单抗阻断免疫细胞上的程序性死亡受体 - 1（PD - 1）抑制性细胞表面分子，可使一部分晚期难治性实体瘤患者的肿瘤消退。我们在一项具有扩展队列的I期研究中报告了接受纳武利尤单抗治疗的晚期肾细胞癌（RCC）患者的临床疗效、生存率和长期安全性。
患者与方法 2008年至2012年间，共有34例既往接受过治疗的晚期RCC患者参与研究，在门诊接受静脉注射纳武利尤单抗（1或10 mg/kg），每两周一次，最长持续96周，并在停药后观察生存率和缓解持续时间。
结果 10例患者（29%）达到客观缓解（根据实体瘤疗效评价标准[1.0版]），中位缓解持续时间为12.9个月；另外9例患者（27%）病情稳定持续超过24周。5例在缓解状态下停药的患者中有3例继续缓解达45周。所有患者（71%接受过2 - 5种既往全身治疗）的中位总生存期为22.4个月；1年、2年和3年生存率分别为71%、48%和44%。18%的患者发生3 - 4级治疗相关不良事件；所有不良事件均可逆。
结论 接受纳武利尤单抗治疗的晚期难治性RCC患者显示出持久的缓解，部分缓解者在停药后仍持续缓解。总生存期令人鼓舞，且毒性通常可控。正在进行的随机临床试验将进一步评估纳武利尤单抗对晚期RCC患者总生存期的影响。
PurposeBlockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts.Patients and MethodsA total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation.ResultsTen patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible.ConclusionPatients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC.