Efficacy of Pemetrexed-Based Chemotherapy in Patients with ROS1 Fusion–Positive Lung Adenocarcinoma Compared with in Patients Harboring Other Driver Mutations.

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Efficacy of Pemetrexed-Based Chemotherapy in Patients with ROS1 Fusion–Positive Lung Adenocarcinoma Compared with in Patients Harboring Other Driver Mutations in East Asian Populations Yen-Fu Chen, MD, Min-Shu Hsieh, MD, Shang-Gin Wu, MD, Yih-Leong Chang, MD, Chong-Jen Yu, MD, PhD, James Chih-Hsin Yang, MD, PhD, Pan-Chyr Yang, MD, PhD, Jin-Yuan Shih, MD, PhD Journal of Thoracic Oncology Volume 11, Issue 7, Pages 1140-1152 (July 2016) DOI: 10.1016/j.jtho.2016.03.022 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 (A) Kaplan-Meier survival curve of progression-free survival (PFS) of pemetrexed treatment. The ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) fusion–positive patients had longer PFS (7.5 months) than did the patients with echinoderm microtubule associated protein like 4 gene (EML4)–anaplastic lymphoma receptor tyrosine kinase gene (ALK) fusion positivity (5.4 months), quadruple-negative status (4.1 months), and epidermal growth factor receptor gene (EGFR) mutation (3.7 months). (B) Kaplan-Meier survival curve of PFS of patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 received first-line pemetrexed combination therapy. The ROS1-fusion positive patients had a relatively favorable PFS (11.7 months) compared with patients with EML4-ALK fusion positivity (6.4 months), EGFR mutation (6.0 months), and quadruple-negative status (5.1 months). (C) Kaplan-Meier survival curve of the PFS of patients with advanced lung adenocarcinoma who received pemetrexed/platinum within the third lines. The ROS1 fusion–positive and EML4-ALK fusion–positive patients had relatively better PFS (11.5 months and 11.7 months, respectively) than did the patients with quadruple-negative status and those with EGFR mutation. (D) Kaplan-Meier survival curve of the PFS of patients with advanced lung adenocarcinoma who received pemetrexed monotherapy. The ROS1 fusion–positive patients had relatively longer PFS (6.8 months) than did the patients with EML4-ALK fusion positivity (4.4 months), quadruple-negative status (2.8 months), and EGFR mutation (2.5 months). Hazard ratios (HRs) and 95% confidence intervals examining the univariate relationship between PFS and molecular subtypes compared with in the quadruple-negative cohort are shown within each inset box. Journal of Thoracic Oncology 2016 11, 1140-1152DOI: (10.1016/j.jtho.2016.03.022) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 (A) Thymidylate synthase (TS) expression (H-score) in patients with different driver mutations. The median (interquartile range) H-scores were 90 (15–200) in ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) fusion–positive tumors, 50 (0–120) in epidermal growth factor receptor gene (EGFR)-mutant tumors, 50 (0–105) in echinoderm microtubule associated protein like 4 gene (EML4)–anaplastic lymphoma receptor tyrosine kinase gene (ALK) fusion–positive tumors, and 60 (0–160) in quadruple-negative tumors. TS expression in patients with different driver mutations was not statistically different (p = 0.182). (B) Progression-free survival (PFS) analysis in patients with low TS expression with an H-score of 50 or lower (n = 111) and high TS expression with an H-score higher than 50 (n = 111). There was no significant survival difference between these two groups (p = 0.789). Median survival time (MST) is expressed in months. The p values were calculated using the log-rank test. Journal of Thoracic Oncology 2016 11, 1140-1152DOI: (10.1016/j.jtho.2016.03.022) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions