Partial Response to Platinum Doublets in Refractory EGFR-Positive Non-Small Cell Lung Cancer Patients after RRx-001: Evidence of Episensitization
Partial Response to Platinum Doublets in Refractory EGFR-Positive Non-Small Cell Lung Cancer Patients after RRx-001: Evidence of Episensitization
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DOI：
10.1159/000443725
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发表时间：
2016-01-01
影响因子：
0.8
通讯作者：
Brzezniak, Christina
中科院分区：
文献类型：
--
作者：
Carter, Corey A.;Oronsky, Bryan T.;Brzezniak, Christina
RRx-001是一种实验性的系统无毒的表观免疫治疗剂，它增强了耐药癌细胞对以前有效的治疗的再敏感作用，目前正在进行几项临床试验的积极研究，这些试验基于对耐药一线或二线方案的顺序或伴随的重新挑战。其中一项试验被命名为三重威胁(NCT02489903)，因为它探索了RRx-001在重新给药之前对三种肿瘤类型--非小细胞肺癌(NSCLC)、小细胞肺癌和高级别神经内分泌肿瘤--的调节或启动效应。最近的一项案例研究描述了RRx-001在难治性EGFR突变的NSCLC肿瘤中的早期单一治疗益处，在这项研究的后续研究中，我们提出了随后的证据，表明RRx-001后再次引入铂对治疗有部分放射学反应。对于50%的EGFR突变的非小细胞肺癌患者，他们使用EGFR酪氨酸激酶抑制剂(没有T790M突变的证据)以及铂类药物和培美曲塞/紫杉烷，没有其他临床确定的治疗方案。在EGFR阳性的非小细胞肺癌患者中，通过使用RRx-001等表观遗传剂重新试验这些疗法，构成了一种使肿瘤“表观敏感”(即通过表观遗传学手段逆转耐药性)并延长总存活率的策略。(C)2016年作者(S)，S.Karger AG，巴塞尔出版
RRx-001, an experimental systemically non-toxic epi-immunotherapeutic agent, which potentiates the resensitization of resistant cancer cells to formerly effective therapies, is under active investigation in several clinical trials that are based on sequential or concomitant rechallenge to resistant first-or second-line regimens. One of these trials is designated TRIPLE THREAT (NCT02489903), because it explores the conditioning or priming effect of RRx-001 on three tumor types - non-small cell lung cancer (NSCLC), small cell lung cancer and high-grade neuroendocrine tumors - prior to re-administration of platinum doublets. In follow-up to a recent case study, which describes early monotherapeutic benefit with RRx-001 in a refractory EGFR-mutated NSCLC tumor, we present subsequent evidence of a radiological partial response to reintroduced platinum doublets after RRx-001. For the 50% of patients with EGFR-mutated NSCLC who progress on EGFR-tyrosine kinase inhibitors (without evidence of a T790M mutations) as well as platinum doublets and pemetrexed/taxane, no other clinically established treatment options exist. A retrial of these therapies in EGFR-positive NSCLC patients via priming with epigenetic agents such as RRx-001 constitutes a strategy to 'episensitize' tumors (i.e. reverse resistance by epigenetic means) and to extend overall survival. (C) 2016 The Author(s) Published by S. Karger AG, Basel