Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1
Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1
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DOI：
10.1158/1078-0432.ccr-16-1741
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发表时间：
2017-04-15
影响因子：
11.5
通讯作者：
Ferte, Charles
中科院分区：
文献类型：
--
作者：
Champiat, Stephane;Dercle, Laurent;Ferte, Charles
目的：虽然免疫检查点抑制剂正在扰乱癌症患者的治疗，但在这些药物下发生快速进展(即超进展性疾病或HPD)的轶事已被描述，这表明这些药物具有潜在的有害影响。在接受抗PD-1/PD-L1治疗的癌症患者中，HPD的患病率、自然病史和预测因素尚不清楚。实验设计：分析在I期临床试验中接受抗PD-1/PD-L1治疗的所有患者(N=218)的病历。比较抗PD-1/PD-L1抗体治疗前后肿瘤生长率(TGR)，以确定肿瘤生长加速的患者。结果：HPD在第一次评估时被定义为RECIST进展，在REF和EXP期间TGR增加2倍。在131名可评估的患者中，12名患者(9%)被认为患有HPD。HPD与基线时较高的肿瘤负荷无关，也与任何特定的肿瘤类型无关。病情进展时，HPD患者的新皮损率低于无HPD的患者(P<；0.05)。HPD与较高的年龄(P<；0.05)和较差的预后(总存活率)有关。有趣的是，REF TGR(治疗前)与抗PD-1/PD-L1(P<；0.05)治疗的反应呈负相关。结论：在接受抗PD-1/PD-L1治疗的患者中，存在一种新的侵袭性超进展模式。这一观察结果引起了人们对使用抗PD-1/PD-L1单一疗法治疗老年患者(>；65岁)的一些担忧，并建议对这一现象进行进一步研究。(C)2016年AACR。
Purpose: While immune checkpoint inhibitors are disrupting the management of patients with cancer, anecdotal occurrences of rapid progression (i.e., hyperprogressive disease or HPD) under these agents have been described, suggesting potentially deleterious effects of these drugs. The prevalence, the natural history, and the predictive factors of HPD in patients with cancer treated by anti-PD-1/PD-L1 remain unknown.Experimental Design: Medical records from all patients (N = 218) prospectively treated in Gustave Roussy by anti-PD-1/PD-L1 within phase I clinical trials were analyzed. The tumor growth rate (TGR) prior ("REFERENCE"; REF) and upon ("EXPERIMENTAL"; EXP) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth. Associations between TGR, clinicopathologic characteristics, and overall survival (OS) were computed.Results: HPD was defined as a RECIST progression at the first evaluation and as a >= 2-fold increase of the TGR between the REF and the EXP periods. Of 131 evaluable patients, 12 patients (9%) were considered as having HPD. HPD was not associated with higher tumor burden at baseline, nor with any specific tumor type. At progression, patients with HPD had a lower rate of new lesions than patients with disease progression without HPD (P < 0.05). HPD is associated with a higher age (P < 0.05) and a worse outcome (overall survival). Interestingly, REF TGR (before treatment) was inversely correlated with response to anti-PD-1/PD-L1 (P < 0.05) therapy.Conclusions: A novel aggressive pattern of hyperprogression exists in a fraction of patients treated with anti-PD-1/PD-L1. This observation raises some concerns about treating elderly patients (>65 years old) with anti-PD-1/PD-L1 monotherapy and suggests further study of this phenomenon. (C) 2016 AACR.