Passaro Antonio, Novello Silvia, Giannarelli Diana, Bria Emilio, Galetta Domenico, Gelibter Alain, Reale Maria Lucia, Carnio Simona, Vita Emanuele, Stefani Alessio, Pizzutilo Pamela, Stati Valeria, Attili Ilaria, de Marinis Filippo
Division of Thoracic Oncology, European Institute of Oncology IRCCS, 20141 Milano, Italy.
Department of Oncology, Università Degli Studi Di Torino-AOU San Luigi Gonzaga, 10043 Orbassano, Italy.
Cancers (Basel). 2021 Jun 11;13(12):2935. doi: 10.3390/cancers13122935.
Pembrolizumab is approved in monotherapy for the first-line (1L) of advanced or metastatic NSCLC patients with high PD-L1 (≥50%). Despite a proportion of patients achieve long-term survival, about one-third of patients experience detrimental survival outcomes, including early death, hyperprogression, and fast progression. The impact of clinical factors on early progression (EP) development has not been widely explored.
We designed a retrospective, multicenter study involving five Italian centers, in patients with metastatic NSCLC with PD-L1 ≥ 50%, treated with Pembrolizumab in a 1L setting. EP was defined as a progressive disease within three months from pembrolizumab initiation. Baseline clinical factors of patients with and without EP were collected and analyzed. Logistic regression was performed to identify clinical factors associated with EP and an EP prognostic score was developed based on the logistic model.
Overall, 321 out of 336 NSCLC patients treated with 1L pembrolizumab provided all the data for the analysis. EP occurred in 137 (42.7%) patients; the median PFS was 3.8 months (95% CI: 2.9-4.7), and median OS was not reached in the entire study population. Sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), steroids, metastatic sites ≥2, and the presence of liver/pleural metastasis were confirmed as independent factors for EP by multivariate analysis. By combining these factors, we developed an EP prognostic score ranging from 0-13, with three-risk group stratification: 0-2 (good prognosis), 3-6 (intermediate prognosis), and 7-13 (poor prognosis). The area under the curve (AUC) of the model was 0.76 (95% CI: 0.70-0.81).
We identified six clinical factors independently associated with EP. We developed a prognostic score model for EP-risk to potentially improve clinical practice and patient selection for 1L pembrolizumab in NSCLC with high PD-L1, in the real-world clinical setting.
帕博利珠单抗被批准用于一线（1L）治疗PD-L1高表达（≥50%）的晚期或转移性非小细胞肺癌（NSCLC）患者。尽管一部分患者实现了长期生存，但约三分之一的患者生存结果不佳，包括早期死亡、超进展和快速进展。临床因素对早期进展（EP）发生的影响尚未得到广泛研究。
我们设计了一项回顾性多中心研究，涉及意大利的五个中心，纳入PD-L1≥50%的转移性NSCLC患者，这些患者接受了1L方案的帕博利珠单抗治疗。EP定义为帕博利珠单抗开始治疗后三个月内出现疾病进展。收集并分析了有和没有EP的患者的基线临床因素。进行逻辑回归以确定与EP相关的临床因素，并基于逻辑模型制定了EP预后评分。
总体而言，336例接受1L帕博利珠单抗治疗的NSCLC患者中有321例提供了全部分析数据。137例（42.7%）患者发生了EP；中位无进展生存期（PFS）为3.8个月（95%CI：2.9 - 4.7），整个研究人群的中位总生存期（OS）未达到。多因素分析证实，性别、东部肿瘤协作组（ECOG）体能状态（PS）、是否使用类固醇、转移部位≥2个以及是否存在肝/胸膜转移是EP的独立影响因素。通过综合这些因素，我们制定了一个范围为0 - 13的EP预后评分，分为三个风险组：0 - 2（预后良好）、3 - 6（预后中等）和7 - 13（预后不良）。该模型的曲线下面积（AUC）为0.76（95%CI：0.70 - 0.81）。
我们确定了六个与EP独立相关的临床因素。我们开发了一个EP风险预后评分模型，以在真实世界临床环境中潜在地改善NSCLC中高PD-L1患者1L帕博利珠单抗治疗的临床实践和患者选择。
