Journal
LUNG CANCER
Volume 147, Issue -, Pages 130-136Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2020.07.016
Keywords
Non-small cell lung cancer; Crizotinib; Effectiveness; First-line treatment; Prognostic factors; Resistance mechanisms
Categories
Funding
- National Natural Science Foundation of China [81972179]
- Zhejiang Provincial Natural Science Foundation [LGF19H160031]
- Key Research and Development Program of Zhejiang Province [2019C03042]
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Introduction: ROS1 rearrangements are seen in 1-2 % of non-small cell lung cancer (NSCLC) patients. The aim of this study was to determine the effectiveness of crizotinib as first-line treatment in patients with ROS1 rearranged NSCLC. Methods: The data of 56 patients with ROS1-rearranged advanced NSCLC who received first-line crizotinib treatment from 5 hospitals in China were retrospectively reviewed. The clinical characteristics, outcomes of first line crizotinib therapy and prognostic factors were evaluated. In addition, mechanisms of resistance to crizotinib were analyzed in a cohort of crizotinib-resistant patients. Results: The median age of the cohort was 53.0 years and most patients (91.1 %) had adenocarcinomas. The median progression free survival (mPFS) after first-line crizotinib therapy was 23.0 months, and the median overall survival (mOS) was 60.0 months. In the univariate analysis, mPFS was significantly shorter in female patients compared to males (12.0 months versus 24.0 months; p = 0.015) and in patients with 0.001).In addition, the mOS was significantly shorter in patients with 0.001). Multivariable analysis further showed that 2 baseline metastatic organ involvement was the only independent prognostic factor of PFS (p = 0.008). Four out of 8 patients (50 %) with crizotinib resistance harbored a G2032R mutation in the ROS1 kinase domain. Conclusions: First-line crizotinib treatment is beneficial in Chinese patients with ROS1-rearranged advanced NSCLC. Resistance to crizotinib correlated with the G2032R mutation in the ROS1 kinase domain.
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