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Characteristics and Outcome of ROS1-Positive Non-Small Cell Lung Cancer Patients in Routine Clinical Practice

 Sehhoon Park  ;  Beung-Chul Ahn  ;  Sung Won Lim  ;  Jong-Mu Sun  ;  Hye Ryun Kim  ;  Min Hee Hong  ;  Se-Hoon Lee  ;  Jin Seok Ahn  ;  Keunchil Park  ;  Yoon La Choi  ;  Byoung Chul Cho  ;  Myung-Ju Ahn 
 JOURNAL OF THORACIC ONCOLOGY, Vol.13(9) : 1373-1382, 2018 
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Carcinoma ; Crizotinib ; Non–small cell lung cancer ; Pemetrexed ; ROS1
INTRODUCTION: ROS1-rearranged NSCLC is classified as a distinct molecular subset of NSCLC with a therapeutic target. ROS1 rearrangement is most often identified in never-smokers with adenocarcinoma and EGFR and ALK receptor tyrosine kinase gene (ALK) wild type. Treatment with tyrosine kinase inhibitors (TKIs), which target the ROS1 kinase domain, is considered the standard of care. TKIs have been shown to have a robust and durable response. However, information regarding the clinical outcomes of TKI treatment, including brain metastasis, remains limited. METHODS: We identified 103 consecutive cases of ROS1-positive NSCLC by using break-apart fluorescence in situ hybridization (n = 84), next-generation sequencing (n = 23), or both (n = 3). Information regarding fusion breakpoints was available for eight patients. Clinical data, including patient characteristics, incidence of brain metastasis, response to chemotherapy, or to TKIs, were retrospectively analyzed. RESULTS: The median patient age was 56 years, and 58.9% of the patients were female. Most of the patients (75.7%) were never-smokers. Adenocarcinoma was predominant (98.1%), and two cases with pleomorphic carcinoma were identified. Sixty percent of patients had an extrathoracic metastatic lesion, and 22% had an intracranial lesion at the initial presentation or at the time of recurrence. The median time to development of brain metastases was 12.0 months (range 2.1-84.1). The most common fusion partner was CD74 molecule gene (CD74), followed by syndecan 4 gene (SDC4), ezrin gene (EZR), tropomyosin 3 gene (TPM3), TRK-fused gene (TFG), zinc finger CCHC-type containing 8 gene (ZCCHC8), sacrolemma associated protein gene (SLMAP), and myosin VC gene (MYO5C). All of these fusion partners preserved the tyrosine kinase domain of ROS1. The median overall survival time was 52.1 months (95% confidence interval [CI]: 23.6-not reached). In the 90 patients who were treated with pemetrexed-based chemotherapy, the overall response rate and progression-free survival time were 53.3% and 8.0 months (95% CI: 6.4-11.7), respectively. The overall response rate and progression-free survival time were 70.7% and 12.7 months (95% CI: 8.1-21.8), respectively, for the 50 patients treated with TKIs. Brain metastasis was more often observed during TKI treatment (15.5%) than during pemetrexed-based chemotherapy (6.7%). CONCLUSIONS: ROS1-positive NSCLC has distinct clinical characteristics, with an effective and durable response to both TKIs and pemetrexed-based chemotherapies. Regardless, given its novel characteristics and distinct clinical responses to conventional chemotherapies and TKIs, the treatment strategy for ROS1-positive NSCLC remains to be further developed.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Ahn, Beung-Chul(안병철) ORCID logo https://orcid.org/0000-0002-2579-2791
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
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