Salvador-Coloma Carmen, Lorente David, Palanca Sarai, Simarro Javier, Mancheño Nuria, Sandoval Juan, Lahoz Agustín, Juan Óscar
Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
Department of Medical Oncology, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
J Thorac Dis. 2018 Mar;10(3):1386-1393. doi: 10.21037/jtd.2018.02.30.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are the standard treatment of advanced, -mutant non-small-cell lung cancer (NSCLC). Usually, radiographic assessment of response to chemotherapy is performed after the patient completes the second course of treatment. The optimal timing of response evaluation for patients receiving EGFR-TKIs is, however, not well-defined. The purpose of this study is to evaluate the association of an early radiological response (ERR) to TKIs by computed tomography (CT) with progression-free survival (PFS) and overall survival (OS) in advanced NSCLC patients with mutations.
mutation status was analyzed retrospectively in a cohort of 360 NSCLC patients' between January 2009 and November 2014. Forty of them received treatment with TKI and therefore were included in the study. Response to TKI therapy was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. ERR was defined as complete response (CR) or partial response (PR) at the first radiographic evaluation performed within 6-8 weeks after the beginning of the treatment.
Activating mutations in the tyrosine kinase domain of the gene were mainly exon 19 deletions. Thirty patients (75%) had ERR, 4 of those patients (10%) showed a PR on early CT achieving a CR in the long-term monitoring. Median PFS was longer in patients experiencing an ERR (10.9 2.4 months; HR: 0.42; 95% CI: 0.19-0.93; P=0.033) than those that did not [stable disease (SD) or progressive disease (PD)]. Median overall survival OS was also significantly increased in patients experiencing ERR (23.2 11.9 months; HR: 0.3; 95% CI: 0.15-0.85; P=0.021).
ERR in patients treated with EGFR TKI therapy is associated with statistically significant PFS and OS, and could be a surrogate marker of efficacy in these patients. Moreover, ERR provides an early identification of patients not benefitting from TKI, despite the presence of activating mutations in which further efforts are needed to improve their prognosis.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）是晚期EGFR突变型非小细胞肺癌（NSCLC）的标准治疗方法。通常，在患者完成第二个疗程的治疗后进行化疗反应的影像学评估。然而，接受EGFR-TKIs治疗的患者进行反应评估的最佳时机尚不清楚。本研究的目的是评估晚期NSCLC患者通过计算机断层扫描（CT）对TKI的早期放射学反应（ERR）与无进展生存期（PFS）和总生存期（OS）之间的关联。
回顾性分析了2009年1月至2014年11月期间360例NSCLC患者队列中的EGFR突变状态。其中40例接受了TKI治疗，因此被纳入研究。根据实体瘤疗效评价标准（RECIST）v1.1定义对TKI治疗的反应。ERR定义为在治疗开始后6-8周内进行的首次影像学评估时的完全缓解（CR）或部分缓解（PR）。
EGFR基因酪氨酸激酶结构域的激活突变主要是外显子19缺失。30例患者（75%）有ERR，其中4例患者（10%）在早期CT上显示PR，在长期监测中达到CR。经历ERR的患者的中位PFS（10.9±2.4个月；HR：0.42；95%CI：0.19-0.93；P=0.033）比未经历ERR的患者[疾病稳定（SD）或疾病进展（PD）]更长。经历ERR的患者的中位总生存期OS也显著增加（23.2±11.9个月；HR：0.3；95%CI：0.15-0.85；P=0.021）。
接受EGFR TKI治疗的患者的ERR与具有统计学意义的PFS和OS相关，并且可能是这些患者疗效的替代标志物。此外，ERR可早期识别出尽管存在激活的EGFR突变但未从TKI中获益的患者，对此需要进一步努力改善其预后。
