Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib The SURTIME Randomized Clinical Trial
Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib The SURTIME Randomized Clinical Trial
复制标题
DOI：
10.1001/jamaoncol.2018.5543
复制
发表时间：
2019-02-01
期刊：
影响因子：
28.4
通讯作者：
Haanen, John
中科院分区：
文献类型：
--
作者：
Bex, Axel;Mulders, Peter;Haanen, John
在临床实践中，原发性转移性肾细胞癌(MRCC)患者已经接受了细胞减少性肾切除术(CN)，然后进行靶向治疗，但最优的手术和系统治疗顺序尚不清楚。目的研究在CN之前接受一段时间的舒尼替尼治疗与在随后立即接受CN治疗相比是否改善了预后。设计、设置和参与者这项随机临床试验于2010年7月14日开始，为3期试验，一直持续到2016年3月24日，中位随访时间为3.3年，本报告的临床截止日期为2017年5月5日。研究对象是具有透明细胞亚型、可切除的原发肿瘤、手术危险因素不超过3个的肾细胞癌患者。对比研究即刻CN和舒尼替尼治疗，以及在无进展的情况下先用CN再CN再接受舒尼替尼治疗的患者。由于应计利润较低，独立数据监测委员会支持报告意向治疗28周无进展率(PFR)。结果5.7年后，99例患者(男80例，女19例；平均年龄60[8.5]岁)结束研究。28周PFR在即刻CN组(n=50)和延迟CN组(n=49)分别为42%和43%(P=.61)。延迟组与即刻组的意向治疗OS风险比为0.57(95%CI，0.34~0.95；P=0.03)，延迟CN组中位OS为32.4个月(95%CI，14.5~65.3个月)，即刻CN组为15.0个月(95%CI，9.3~29.5个月)。在延期的CN组中，49名患者中有48名(98%；95%CI，89%-100%)接受了舒尼替尼治疗，而50名患者中有40名(80%；95%CI，67%-89%)接受了舒尼替尼治疗。在延迟CN组中，在计划CN之前的全身进展导致14名患者(29%；95%CI，18%-43%)按方案建议不接受肾切除术。结论延迟CN和相关性CN不能改善28周的PFR。采用延期治疗的患者中，接受舒尼替尼治疗的患者更多，OS结果也更高。在计划CN之前，用舒尼替尼预治疗可能会识别出对全身治疗有固有抵抗的患者。这一证据补充了随机临床试验的最新数据，为需要舒尼替尼的原发性透明细胞肾细胞癌患者的治疗决策提供信息。
IMPORTANCE In clinical practice, patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown.OBJECTIVE To examine whether a period of sunitinib therapy before CN improves outcome compared with immediate CN followed by sunitinib.DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial began as a phase 3 trial on July 14, 2010, and continued until March 24, 2016, with a median follow-up of 3.3 years and a clinical cutoff date for this report of May 5, 2017. Patients with mRCC of clear cell subtype, resectable primary tumor, and 3 or fewer surgical risk factors were studied.INTERVENTIONS Immediate CN followed by sunitinib therapy vs treatment with 3 cycles of sunitinib followed by CN in the absence of progression followed by sunitinib therapy.MAIN OUTCOMES AND MEASURES Progression-free survival was the primary end point, which needed a sample size of 458 patients. Because of poor accrual, the independent data monitoring committee endorsed reporting the intention-to-treat 28-week progression-free rate (PFR) instead. Overall survival (OS), adverse events, and postoperative progression were secondary end points.RESULTS The study closed after 5.7 years with 99 patients (80 men and 19 women; mean [SD] age, 60 [8.5] years). The 28-week PFR was 42% in the immediate CN arm (n = 50) and 43% in the deferred CN arm (n = 49) (P = .61). The intention-to-treat OS hazard ratio of deferred vs immediate CN was 0.57 (95% CI, 0.34-0.95; P = .03), with a median OS of 32.4 months (95% CI, 14.5-65.3 months) in the deferred CN arm and 15.0 months (95% CI, 9.3-29.5 months) in the immediate CN arm. In the deferred CN arm, 48 of 49 patients (98%; 95% CI, 89%-100%) received sunitinib vs 40 of 50 (80%; 95% CI, 67%-89%) in the immediate arm. Systemic progression before planned CN in the deferred CN arm resulted in a per-protocol recommendation against nephrectomy in 14 patients (29%; 95% CI, 18%-43%).CONCLUSIONS AND RELEVANCE Deferred CN did not improve the 28-week PFR. With the deferred approach, more patients received sunitinib and OS results were higher. Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned CN. This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib.