Phase II Randomized Trial Comparing Sequential First-Line Everolimus and Second-Line Sunitinib Versus First-Line Sunitinib and Second-Line Everolimus in Patients With Metastatic Renal Cell Carcinoma
Phase II Randomized Trial Comparing Sequential First-Line Everolimus and Second-Line Sunitinib Versus First-Line Sunitinib and Second-Line Everolimus in Patients With Metastatic Renal Cell Carcinoma
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DOI：
10.1200/jco.2013.54.6911
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发表时间：
2014-09-01
影响因子：
45.3
通讯作者：
Knox, Jennifer J.
中科院分区：
文献类型：
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作者：
Motzer, Robert J.;Barrios, Carlos H.;Knox, Jennifer J.
PurposeA多中心，随机II期临床试验，RECORD-3，进行比较一线依维莫司，其次是舒尼替尼在进展与标准序列的一线舒尼替尼，其次是依维莫司在转移性肾细胞cancer.Patients和MethodsRECORD-3采用交叉治疗设计。主要目的是评估一线依维莫司与一线舒尼替尼相比的无进展生存期（PFS）非劣效性。次要终点包括合并PFS为每个序列，总生存期（OS），和safety.ResultsOf 471例入组患者，238被随机分配到一线依维莫司其次舒尼替尼，和233被随机分配到一线舒尼替尼其次依维莫司。未达到主要终点;一线依维莫司的中位PFS为7.9个月，一线舒尼替尼为10.7个月（风险比[HR]，1.4; 95% CI，1.2 - 1.8）。在停止一线治疗的患者中，108例（45%）从依维莫司交叉至二线舒尼替尼，99例（43%）从舒尼替尼交叉至二线依维莫司。依维莫司序贯舒尼替尼的中位合并PFS为21.1个月，舒尼替尼序贯依维莫司的中位合并PFS为25.8个月（HR，1.3; 95% CI，0.9 - 1.7）。序贯依维莫司，然后舒尼替尼的中位OS为22.4个月，序贯舒尼替尼，然后依维莫司的中位OS为32.0个月（HR，1.2; 95% CI，0.9 - 1.6）。一线依维莫司或舒尼替尼治疗期间常见的治疗后出现的不良事件是口腔炎（分别为53%和57%），疲劳（分别为45%和51%），腹泻（分别为38%和57%）。试验结果支持标准的一线治疗模式舒尼替尼，然后依维莫司进展。(C)2014年美国临床肿瘤学会
PurposeA multicenter, randomized phase II trial, RECORD-3, was conducted to compare first-line everolimus followed by sunitinib at progression with the standard sequence of first-line sunitinib followed by everolimus in patients with metastatic renal cell carcinoma.Patients and MethodsRECORD-3 used a crossover treatment design. The primary objective was to assess progression-free survival (PFS) noninferiority of first-line everolimus compared with first-line sunitinib. Secondary end points included combined PFS for each sequence, overall survival (OS), and safety.ResultsOf 471 enrolled patients, 238 were randomly assigned to first-line everolimus followed by sunitinib, and 233 were randomly assigned to first-line sunitinib followed by everolimus. The primary end point was not met; the median PFS was 7.9 months for first-line everolimus and 10.7 months for first-line sunitinib (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.8). Among patients who discontinued first-line, 108 (45%) crossed over from everolimus to second-line sunitinib, and 99 (43%) crossed over from sunitinib to second-line everolimus. The median combined PFS was 21.1 months for sequential everolimus then sunitinib and was 25.8 months for sequential sunitinib then everolimus (HR, 1.3; 95% CI, 0.9 to 1.7). The median OS was 22.4 months for sequential everolimus and then sunitinib and 32.0 months for sequential sunitinib and then everolimus (HR, 1.2; 95% CI, 0.9 to 1.6). Common treatment-emergent adverse events during first-line everolimus or sunitinib were stomatitis (53% and 57%, respectively), fatigue (45% and 51%, respectively), and diarrhea (38% and 57%, respectively).ConclusionEverolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy. The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression. (C) 2014 by American Society of Clinical Oncology