比较 II 期临床试验中接受 pembrolizumab 治疗的晚期黑色素瘤患者的 RECIST 1.1 和 iRECIST。
Comparing RECIST 1.1 and iRECIST in advanced melanoma patients treated with pembrolizumab in a phase II clinical trial.
机构信息
Columbia University Irving Medical Center, 622 W 168th Street, PHB-1, New York, NY, 10032, USA.
Merck & Co. Pharmaceutical, Warrington, PA, USA.
出版信息
Eur Radiol. 2021 Apr;31(4):1853-1862. doi: 10.1007/s00330-020-07249-y. Epub 2020 Sep 30.
OBJECTIVES
To compare tumor best overall response (BOR) by RECIST 1.1 and iRECIST, to explore the incidence of pseudoprogression in melanoma treated with pembrolizumab, and to assess the impact of pseudoprogression on overall survival (OS).
METHODS
A total of 221 patients with locally advanced/unresectable melanoma who received pembrolizumab as part of KEYNOTE-002 trial were included in this study. Radiological assessment of imaging was centrally reviewed to assess tumor response. Incidence of discordance in BOR between RECIST 1.1 and iRECIST as well as rate of pseudoprogression were measured. OS of patients with pseudoprogression was compared with that of those with uncontrolled disease.
RESULTS
Of the 221 patients in this cohort, 136 patients developed PD as per RECIST v1.1 and 78 patients with PD continued treatment and imaging beyond initial RECIST 1.1-defined PD. Among the 78 patients who continued therapy and imaging post-progression, RECIST 1.1 and iRECIST were discordant in 10 patients (12.8%) and pseudoprogression was encountered in 14 patients (17.9%). OS of patients with pseudoprogression was longer than that of patients with uncontrolled disease/true progression (29.9 months versus 8.0 months, p value < 0.001).
CONCLUSIONS
Effectiveness of immunotherapy in clinical trials depends on the criterion used to assess tumor response (RECIST 1.1 vs iRECIST) with iRECIST being more appropriate to detect pseudoprogression and potentially prevent premature termination of effective therapy. Pseudoprogression was associated with improved OS in comparison with that of patients with uncontrolled disease.
KEY POINTS
• Discordance between iRECIST and RECIST 1.1 was found in 12.8% of unresectable melanoma patients on pembrolizumab who continued therapy beyond initial RECIST 1.1-defined progression. • Pseudoprogression, captured with iRECIST, occurred in 17.9% and was significantly associated with improved overall survival in comparison with uncontrolled disease.
目的
比较 RECIST 1.1 和 iRECIST 的肿瘤最佳总体缓解（BOR），探索 pembrolizumab 治疗黑色素瘤中的假性进展发生率，并评估假性进展对总生存期（OS）的影响。
方法
本研究共纳入 221 例接受 pembrolizumab 治疗的局部晚期/不可切除黑色素瘤患者，这些患者均来自 KEYNOTE-002 试验。对影像学检查进行中心评估，以评估肿瘤反应。测量 RECIST 1.1 和 iRECIST 之间 BOR 不一致的发生率以及假性进展的发生率。比较假性进展患者和未控制疾病患者的 OS。
结果
在本队列的 221 例患者中，根据 RECIST v1.1，136 例患者出现 PD，78 例 PD 患者继续接受治疗，并在初始 RECIST 1.1 定义的 PD 后进行影像学检查。在继续治疗和影像学检查的 78 例患者中，10 例（12.8%）患者的 RECIST 1.1 和 iRECIST 不一致，14 例（17.9%）患者出现假性进展。假性进展患者的 OS 长于未控制疾病/真正进展患者（29.9 个月与 8.0 个月，p 值<0.001）。
结论
临床试验中免疫治疗的疗效取决于评估肿瘤反应的标准（RECIST 1.1 与 iRECIST），iRECIST 更适合检测假性进展，从而有可能防止过早终止有效治疗。与未控制疾病患者相比，假性进展与 OS 改善相关。
关键点
在继续接受初始 RECIST 1.1 定义的进展后治疗的不可切除黑色素瘤患者中，发现 iRECIST 与 RECIST 1.1 之间存在 12.8%的不一致。
用 iRECIST 检测到假性进展，发生率为 17.9%，与未控制疾病相比，显著改善了总生存期。
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