Efficacy of of Pemetrexed-Based Chemotherapy in Patients with ROS1 Fusion-Positive Lung Adenocarcinoma Compared with in Patients Harboring Other Driver Mutations in East Asian Populations
Efficacy of of Pemetrexed-Based Chemotherapy in Patients with ROS1 Fusion-Positive Lung Adenocarcinoma Compared with in Patients Harboring Other Driver Mutations in East Asian Populations
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东亚人群中ROS1融合阳性肺腺癌患者与携带其他驱动基因突变患者相比，培美曲塞化疗方案的疗效
DOI：
10.1016/j.jtho.2016.03.022
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发表时间：
2016-07-01
影响因子：
20.4
通讯作者：
Shih, Jin-Yuan
中科院分区：
文献类型：
--
作者：
Chen, Yen-Fu;Hsieh, Min-Shu;Shih, Jin-Yuan
简介：基于培美曲塞的化疗对具有新型 ROS 原癌基因 1、受体酪氨酸激酶基因 (ROS1) 致癌重排的晚期肺腺癌患者的疗效尚不清楚。本研究旨在比较基于培美曲塞的化疗对晚期 ROS1 融合肺腺癌患者的疗效与对具有不同驱动突变的患者的疗效。方法：我们回顾性筛选了筛选表皮生长因子受体基因（EGFR）突变、棘皮动物微管相关蛋白样 4 基因（EML4）-间变性淋巴瘤受体酪氨酸激酶基因（ALK）易位的晚期肺腺癌患者、Kirsten 大鼠肉瘤病毒癌基因同源基因 (KRAS) 突变，以及使用多重逆转录酶聚合酶链反应进行 ROS1 融合。接受培美曲塞治疗的患者被纳入进一步分析。将ROS1融合阳性肺腺癌患者的人口统计数据、临床结果和胸苷酸合酶免疫染色（H评分）与携带EGFR突变、EML4-ALK融合、KRAS突变和四阴性的患者进行比较。结果：共有253例晚期肺腺癌患者接受了基于培美曲塞的治疗方案，并根据分子发现进行分类如下： 102 名患者 (40.3%) 存在 EGFR 突变，32 名患者 (12.6%) 存在 EML4-ALK 易位，3 名患者 (1.2%) 存在 KRAS 突变，19 名患者 (7.5%) 存在 ROS1 融合，97 名患者 (38.3%) 存在四阴性状态。与携带其他驱动突变的患者相比，ROS1融合的患者具有更好的总体缓解率（57.9%，p = 0.026）、疾病控制率（89.5%，p = 0.033）和更长的无进展生存期（7.5个月，p = 0.003）。然而，不同分子亚型肺腺癌患者的胸苷酸合酶H评分与培美曲塞治疗的反应无关。结论：ROS1融合阳性可能是肺腺癌患者培美曲塞治疗的有利因素。 (C) 2016 年国际肺癌研究协会。由爱思唯尔公司出版。保留所有权利。
Introduction: The efficacy of pemetrexed-based chemotherapy in patients with advanced lung adenocarcinoma with novel ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) oncogenic rearrangement is unclear. This study aimed to compare the efficacy of pemetrexed-based chemotherapy in patients with advanced ROS1-fusion lung adenocarcinoma with its efficacy in those having different driver mutations.Methods: We retrospectively identified patients with advanced lung adenocarcinoma who were screened for epidermal growth factor receptor gene (EGFR) mutations, echinoderm microtubule associated protein like 4 gene (EML4)-anaplastic lymphoma receptor tyrosine kinase gene (ALK) translocation, Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutations, and ROS1 fusion by using multiplex reverse-transcriptase polymerase chain reaction. Patients who received pemetrexed-based therapy were enrolled for further analysis. The demographic data, clinical outcomes, and thymidylate synthase immunostaining (H-score) of patients with ROS1 fusion-positive lung adenocarcinomas were compared with those of patients harboring EGFR mutations, EML4-ALK fusion, KRAS mutations, and quadruple negativity.Results: A total of 253 patients with advanced lung adenocarcinoma received a pemetrexed-based regimen and were classified on the basis of molecular findings as follows: 102 patients (40.3%) with EGFR mutations, 32 patients (12.6%) with EML4-ALK translocation, three patients (1.2%) with KRAS mutations, 19 patients (7.5%) with ROS1 fusion, and 97 patients (38.3%) with quadruple-negative status. Patients with ROS1 fusion had a better overall response rate (57.9%, p = 0.026), disease control rate (89.5%, p = 0.033), and longer progression-free survival (7.5 months, p = 0.003) compared with patients harboring other driver mutations. However, the H-score of thymidylate synthase was not associated with the response to pemetrexed therapy in patients with different molecular subtypes of lung adenocarcinoma.Conclusions: ROS1 fusion positivity is probably a favorable factor of pemetrexed-based therapy for patients with lung adenocarcinoma. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.