Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab
Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab
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DOI：
10.1200/jco.2015.64.0391
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发表时间：
2016-05-01
影响因子：
45.3
通讯作者：
Wolchok, Jedd D.
中科院分区：
文献类型：
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作者：
Hodi, F. Stephen;Hwu, Wen-Jen;Wolchok, Jedd D.
我们评估了在Lb期Keynote-001研究(临床试验信息：NCT01295827)中接受培溴利珠单抗治疗的晚期黑色素瘤患者的非典型反应模式以及根据免疫相关反应标准(IRRC)和实体肿瘤反应评估标准1.1(RECIST v1.1)测量的总体生存率和最佳总体反应之间的关系。非典型反应是通过集中评估IRRC数据在>；=28周成像的患者中确定的。假性进展的定义是：在12周(早期)或12周后(延迟)的任何评估中，肿瘤负担增加了25%，在下一次评估中未确认为进展性疾病。根据IRRC和RECIST v1.1对疗效进行集中评估。结果：在纳入的655例黑色素瘤患者中，327例获得了28周的影像随访。在这327名患者中，24名(7%)有不典型的反应(15名[5%]早期假性进展，9名[3%]假性进展延迟)。在存活12周的592名患者中，84名(14%)根据RECIST V1.1经历了进展性疾病，但根据IRRC经历了非进展性疾病。根据RECIST V1.1和IRRC标准，非进展性疾病患者两年总生存率为77.6%(n=331)，非进展性疾病患者两年总生存率为37.5%(n=84)，两种标准进展性疾病患者两年总生存率为17.3%(n=177)。根据生存分析，传统的RECIST可能低估了约15%患者使用培溴利珠单抗的益处；修改后的标准允许根据RECIST v1.1进行超过初始进展的治疗，可能会防止过早停止治疗。(C)2016年度美国临床肿瘤学会
PurposeWe evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase lb KEYNOTE-001 study (clinical trial information: NCT01295827).Patients and MethodsPatients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with >= 28 weeks of imaging. Pseudoprogression was defined as >= 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1.ResultsOf the 655 patients with melanoma enrolled, 327 had> 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived >= 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per both criteria (n = 177).ConclusionAtypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment. (C) 2016 by American Society of Clinical Oncology