Rocha Pedro, Ramal Didac, Ripoll Enric, Moliner Laura, Corbera Alex, Hardy-Werbin Max, Orrillo Mayra, Taus Álvaro, Zuccarino Flavio, Gibert Joan, Perera-Bel Júlia, Casadevall David, Arriola Edurne
Medical Oncology Department, Hospital del Mar, Barcelona, Spain.
Radiology Department, Hospital del Mar, Barcelona, Spain.
JTO Clin Res Rep. 2020 Oct 28;2(1):100115. doi: 10.1016/j.jtocrr.2020.100115. eCollection 2021 Jan.
Hyperprogressive disease (HPD) as a consequence of immune checkpoint inhibitors in NSCLC has been reported in multiple studies. However, inconsistent results in incidence and survival outcomes within studies, together with different assessment methods, have led to increasing controversy regarding the concept of HPD.
Consecutive patients treated with nivolumab (N = 42) or docetaxel (N = 37) were evaluated. HPD was quantified by applying three different methods (tumor growth rate [TGR], tumor growth kinetics [TGK], and Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]). HPD rates were compared between and within both cohorts using the different methods.
Using TGR, TGK, and RECIST 1.1, we identified seven (16.7%), seven (16.7%), and six (14.3%) patients with HPD in the nivolumab cohort and three (8.1%), four (10.8%), and five (13.6%) in the docetaxel cohort, respectively. We observed a higher concordance between TGR and TGK (90.1%) compared with RECIST 1.1 (31.3% and 37.5% with TGR and TGK, respectively). We found no significant differences in the overall survival between patients with progressive disease and HPD in either cohort.
TGR and TGK revealed high concordance rates for identifying patients with HPD in NSCLC. The incidence of HPD was numerically higher in patients treated with immune checkpoint inhibitors. Standardization of methods for measuring HPD and its exploration in larger studies are needed to establish its clinical meaning in NSCLC.
多项研究报道了免疫检查点抑制剂导致非小细胞肺癌（NSCLC）患者出现超进展性疾病（HPD）。然而，各研究中HPD的发生率和生存结果不一致，再加上评估方法不同，导致关于HPD概念的争议日益增加。
对连续接受纳武利尤单抗治疗（N = 42）或多西他赛治疗（N = 37）的患者进行评估。通过应用三种不同方法（肿瘤生长率 [TGR]、肿瘤生长动力学 [TGK] 和实体瘤疗效评价标准第1.1版 [RECIST 1.1]）对HPD进行量化。使用不同方法比较两个队列之间及队列内部的HPD发生率。
使用TGR、TGK和RECIST 1.1，我们在纳武利尤单抗队列中分别确定了7例（16.7%）、7例（16.7%）和6例（14.3%）HPD患者，在多西他赛队列中分别确定了3例（8.1%）、4例（10.8%）和5例（13.6%）HPD患者。我们观察到，与RECIST 1.1相比，TGR和TGK之间的一致性更高（分别为90.1%，与TGR和TGK的一致性分别为31.3%和37.5%）。我们发现，两个队列中疾病进展患者和HPD患者的总生存期均无显著差异。
TGR和TGK在识别NSCLC中HPD患者方面显示出较高的一致性率。接受免疫检查点抑制剂治疗的患者中HPD的发生率在数值上更高。需要对测量HPD的方法进行标准化，并在更大规模的研究中进行探索，以确定其在NSCLC中的临床意义。
