"PROBE"ing the Role of Cytoreductive Nephrectomy in Advanced Renal Cancer.
"PROBE"ing the Role of Cytoreductive Nephrectomy in Advanced Renal Cancer.
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DOI：
10.3233/kca-210010
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发表时间：
2022-03-15
期刊：
影响因子：
--
通讯作者：
Vaishampayan U
中科院分区：
文献类型：
--
作者：
Bell H;Cotta BH;Salami SS;Kim H;Vaishampayan U
西南肿瘤学组织(SWOG)1931年的试验，也被称为PROBE(ClinicalTrials.gov标识：NCT04510597)是一项第三阶段研究，评估细胞减少性肾切除术(CN)在转移性肾细胞癌(RCC)中的作用。与肾切除术后复发转移的患者相比，出现同步转移的肾癌患者的生存期较短。以前，当使用基于干扰素的系统治疗时，CN与生存改善有关。在抗血管治疗方面，一项前瞻性随机临床试验显示CN没有任何益处。基于免疫检查点的联合治疗现在已经成为肾癌一线治疗的标准护理。肾切除或一期切除在以免疫检查点为基础的系统治疗中的作用尚未得到评估。肾切除的顺序和最佳时机也没有确定。探索性研究设计试图回答在基于免疫检查点的联合方案的背景下，CN是否对肾癌的总体生存结果有影响的问题。这项研究需要从系统治疗开始；在研究启动时，FDA批准的任何一种基于免疫治疗的方案都是允许的。在治疗9-12周时评估病情和反应，然后将同意的患者随机分为接受CN或继续系统治疗的1：1。病情进展迅速的患者被认为没有资格进行随机分组，因为他们需要在系统治疗中进行切换。只要两组患者都能耐受治疗并继续获得临床益处，他们就应该继续进行系统治疗。作为预测生物标记物的生活质量、肿瘤基因组检测、微生物组学、放射组学和循环肿瘤DNA评估被计划作为研究相关性。研究假设是，在开始基于系统免疫检查点的综合治疗后，当手术进行时，CN将改善同步转移的肾癌的OS。导致生存改善的一个潜在机制是原发肿瘤使更广泛的抗原扩散和更高的新抗原负载量增强了免疫治疗的效果。CN在最初的系统治疗后将有助于选择最有可能受益的患者亚群，并可能使原发肿瘤内的免疫耐药克隆得以根除。
The Southwest Oncology Group (SWOG)1931 trial, also known as PROBE (ClinicalTrials.gov Identifier: NCT04510597) is a phase III study evaluating the role of cytoreductive nephrectomy (CN) in metastatic renal cell cancer (RCC). Kidney cancer presenting with synchronous metastases has demonstrated shorter survival outcome compared to the patients relapsing with metastases after nephrectomy. Previously, CN has been associated with survival improvement when interferon-based systemic therapy was used. In the setting of antivascular therapy sunitinib, a prospective randomized clinical trial demonstrated no benefit of CN. Immune checkpoint-based combination therapy has now become the standard-of-care in the frontline setting for RCC. The role of nephrectomy or primary resection has not been evaluated in the setting of immune checkpoint-based systemic therapy. The sequence and optimal timing of nephrectomy is also not established. The PROBE study design attempts to answer the question whether CN has an impact on overall survival outcomes in RCC within the context of immune checkpoint-based combination regimens. The study requires starting with systemic therapy; any one of the FDA approved immunotherapy-based regimens at the time the study was activated are permitted. The disease status and response are evaluated at 9–12 weeks of therapy and then consented patients are randomized 1:1 to receive CN or to continue systemic therapy. The patients who have rapid disease progression are considered ineligible for randomization as they need a switch in systemic therapy. Both groups should continue systemic therapy as long as they are tolerating the treatment and continuing to derive clinical benefit. Quality-of-life, tumor genomic testing, microbiome, radiomics and circulating tumor DNA assessments as predictive biomarkers are planned as study correlatives. The study hypothesis is that CN will improved OS in synchronous metastatic RCC when surgery is performed after starting systemic immune checkpoint-based combination therapy. A potential mechanism leading to improved survival is the broader antigen spread and higher neoantigen load enabled by the primary tumor enhancing the efficacy of the immune therapy. CN after initial systemic therapy would help select the patient subset most likely to benefit and will potentially enable eradication of immune resistant clones within the primary tumor.
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影响因子：
5.2
作者：
Poprach A;Holanek M;Chloupkova R;Lakomy R;Stanik M;Fiala O;Melichar B;Kopeckova K;Zemanova M;Kiss I;Penka I;Bohosova J;Buchler T
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