期刊
JOURNAL OF THORACIC ONCOLOGY
卷 11, 期 7, 页码 1140-1152出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jtho.2016.03.022
关键词
EGFR mutation; EML4-ALK fusion; KRAS mutation; pemetrexed-based therapy; ROS1 fusion
资金
- National Science Council, Taiwan [104-2314-B-002-172-MY3]
- Department of Health, Executive Yuan, Taiwan [NHRI-EX104-10421BI]
- National Taiwan University [104R7601-3]
- National Taiwan University Hospital [104-S2675, 104-FTN09]
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.
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