Adjuvant Treatment for High-Risk Clear Cell Renal Cancer: Updated Results of a High-Risk Subset of the ASSURE Randomized Trial.
Adjuvant Treatment for High-Risk Clear Cell Renal Cancer: Updated Results of a High-Risk Subset of the ASSURE Randomized Trial.
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DOI：
10.1001/jamaoncol.2017.0076
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发表时间：
2017-09-01
期刊：
影响因子：
28.4
通讯作者：
Choueiri TK
中科院分区：
文献类型：
--
作者：
Haas NB;Manola J;Dutcher JP;Flaherty KT;Uzzo RG;Atkins MB;DiPaola RS;Choueiri TK
鉴于最近发表的750名患者的舒尼替尼辅助试验结果显示无病生存期（DFS）得到改善，治疗高危患者的适当策略尚不清楚。我们试图确定在ASSURE试验（在切除的不利肾细胞癌[RCC]中辅助舒尼替尼或索拉非尼与安慰剂）中，高风险（pT 3，pT 4，淋巴结阳性）透明细胞肾癌（ccRCC）患者服用活性药物是否具有改善的无病生存获益，这是迄今为止发表的最大的辅助试验。在分期与其他高风险辅助治疗试验相当的患者中，评价随机接受舒尼替尼或索拉非尼vs安慰剂治疗的ccRCC高风险患者的DFS和总生存期（OS）。计算了美国和加拿大合作组中1069例患者激活后10年的DFS和OS，这些患者为2006年至2010年期间在双盲随机安慰剂对照III期试验中累积的ccRCC组织学和pT 3、pT 4或淋巴结阳性疾病的高风险患者。还对接受舒尼替尼或索拉非尼治疗的患者进行了剂量四分位数的结局分析。患者接受1年的辅助舒尼替尼（50 mg），索拉非尼（800 mg），每日或等效安慰剂。对患者每日舒尼替尼（37.5 mg）、索拉非尼（400 mg）或等效安慰剂不耐受的研究进行了修订，如果未发生严重不良反应，则强制剂量递增。无病生存期，定义为从随机化至复发、第二原发癌或死亡的时间。在1069例患者中，358例（243例[67.9%]男性，115例[32.1%]女性）接受舒尼替尼，355例（248例[69.9%]男性，107例[30.1%]女性）接受索拉非尼，356例（254例[71.3%]男性，102例[28.7%]女性）接受安慰剂作为辅助治疗。各组的平均（SD）年龄分别为58.3（10.6）岁、56.8（10.3）岁和57.5（10.4）岁。舒尼替尼、索拉非尼和安慰剂组的5年DFS率分别为47.7%、49.9%和50.0（舒尼替尼vs安慰剂的HR为0.94;索拉非尼vs安慰剂的HR为0.90; 97.5%CI为0.71-1.14），5年OS分别为75.2%、80.2%和76.5%（舒尼替尼vs安慰剂的HR，1.06; 97.5%CI，0.78-1.45; P = .66;索拉非尼vs安慰剂的HR，0.80; 97.5%CI，0.58-1.11; P = .12）。剂量四分位数无差异。肿瘤的预后类别和治疗的剂量强度都没有改变这一高危ccRCC患者人群中DFS或OS的差异。clinicaltrials.gov标识符：NCT 00326898
Given recently published results of a 750-patient adjuvant sunitinib trial showing improved disease-free survival (DFS), the appropriate strategy for treating high-risk patients is unclear. We sought to determine whether there is improved disease-free survival benefit to taking the active drug in patients with high-risk (pT3, pT4, node-positive) clear cell renal cancer (ccRCC) in the ASSURE trial (adjuvant sunitinib or sorafenib vs placebo in resected unfavorable renal cell carcinoma [RCC]), the largest adjuvant trial published to date. To evaluate DFS and overall survival (OS) in ccRCC high-risk patients randomized to sunitinib or sorafenib vs placebo among patients with stages comparable to other high-risk adjuvant trials. The DFS and OS at 10 years postactivation were calculated for 1069 patients in US and Canadian cooperative groups with high-risk patients who had ccRCC histology and pT3, pT4, or node-positive disease accrued between 2006 and 2010 to the double-blind randomized placebo-controlled phase 3 trial. Outcome analyses by dose quartiles of these patients receiving sunitinib or sorafenib were also performed. Patients received 1 year of adjuvant sunitinib (50 mg), sorafenib (800 mg) daily, or equivalent placebo. The study was amended for patient intolerance to sunitinib (37.5 mg), sorafenib (400 mg) daily, or equivalent placebo with mandatory dose escalation if no serious adverse effects were experienced. Disease-free survival, defined as time from randomization to recurrence, second primary cancer, or death. Of 1069 patients, 358 (243 [67.9%] men, 115 [32.1%] women) received sunitinib, 355 (248 [69.9%] men, 107 [30.1%] women) received sorafenib, and 356 (254 [71.3%] men, 102 [28.7%] women) received placebo as adjuvant therapy. The mean (SD) age for each group was 58.3 (10.6) years, 56.8 (10.3) years, and 57.5 (10.4) years, respectively. Five-year DFS rates were 47.7%, 49.9%, and 50.0%, respectively for sunitinib, sorafenib, and placebo (HR, 0.94 for sunitinib vs placebo; and HR, 0.90; 97.5%CI, 0.71–1.14 for sorafenib vs placebo), with 5-year OS of 75.2%, 80.2%, and 76.5%(HR, 1.06; 97.5%CI, 0.78–1.45; P = .66, sunitinib vs placebo; and HR, 0.80; 97.5%CI, 0.58–1.11; P = .12 for sorafenib vs placebo). There was no difference by dose quartile. Neither prognostic category of the tumor nor dose intensity of therapy altered the lack of difference in DFS or OS in this population of patients with high-risk ccRCC. clinicaltrials.gov Identifier: NCT00326898
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DOI：
10.1016/s0140-6736(16)00559-6
发表时间：
2016-05-14
期刊：
Lancet (London, England)
影响因子：
--
作者：
Haas NB;Manola J;Uzzo RG;Flaherty KT;Wood CG;Kane C;Jewett M;Dutcher JP;Atkins MB;Pins M;Wilding G;Cella D;Wagner L;Matin S;Kuzel TM;Sexton WJ;Wong YN;Choueiri TK;Pili R;Puzanov I;Kohli M;Stadler W;Carducci M;Coomes R;DiPaola RS
通讯作者：
DiPaola RS
影响因子：
158.5
作者：
Ravaud, A.;Motzer, R. J.;Patard, J. -J.
通讯作者：
Patard, J. -J.
影响因子：
6.6
作者：
Lam, JS;Shvarts, O;Belldegrun, AS
通讯作者：
Belldegrun, AS
影响因子：
6.2
作者：
Kim, Simon P.;Crispen, Paul L.;Leibovich, Bradley C.
通讯作者：
Leibovich, Bradley C.
影响因子：
5.8
作者：
Pal, Sumanta K.;Haas, Naomi B.
通讯作者：
Haas, Naomi B.