title: Clinical outcomes of advanced non-small-cell lung cancer patients with EGFR mutation, ALK rearrangement and EGFR/ALK co-alterations.
abstract: The co-occurrence of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements constitutes a rare molecular subtype of non-small-cell lung cancer (NSCLC). Herein, we assessed the clinical outcomes and incidence of acquired resistance to tyrosine kinase inhibitors (TKIs) in this subtype. So we enrolled 118 advanced NSCLC treated with TKIs. EGFR mutations and ALK rearrangements were detected by DNA sequencing or Scorpion amplification refractory mutation system and fluorescence in situ hybridization respectively. Immunohistochemistry was used to evaluate the activation of associated proteins. We found that nine in ten patients with EGFR/ALK co-alterations had good response with first-line EGFR TKI, and the objective response rate (ORR) of EGFR TKIs was 80% (8/10) for EGFR/ALK co-altered and 65.5% (55/84) for EGFR-mutant (P = 0.57), with a median progression-free survival (PFS) of 11.2 and 13.2 months, (hazard ratio [HR]=0.95, 95% [CI], 0.49-1.84, P= 0.87). ORR of crizotinib was 40% (2/5) for EGFR/ALK co-altered and 73.9% (17/23) for ALK-rearranged (P= 0.29), with a median PFS of 1.9 and 6.9 months (hazard ratio [HR], 0.40; 95% [CI] 0.15-1.10, P = 0.08). The median overall survival (OS) was 21.3, 23.7, and 18.5 months in EGFR-mutant, ALK-rearranged, and EGFR/ALK co-altered (P= 0.06), and there existed a statistically significant difference in OS between ALK-rearranged and EGFR/ALK co-altered (P=0.03). Taken together, the first-line EGFR-TKI might be the reasonable care for advanced NSCLC harbouring EGFR/ALK co-alterations, whether or nor to use sequential crizotinib should be guided by the status of ALK rearrangement and the relative level of phospho-EGFR and phospho-ALK.
authors.affiliation: Southern Medical University, Guangzhou, 510515, China.|Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.|Medical Research Center, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Lou
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.|Medical Research Center, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Xu-Chao
authors.initials: XC
authors.lastname: Zhang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Hua-Jun
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Li-Xu
authors.initials: LX
authors.lastname: Yan
authors.affiliation: Medical Research Center, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Medical Research Center, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.affiliation: Medical Research Center, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Tu
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Yan
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Chong-Rui
authors.initials: CR
authors.lastname: Xu
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Ben-Yuan
authors.initials: BY
authors.lastname: Jiang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Bin-Chao
authors.initials: BC
authors.lastname: Wang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Bai
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Wen-Zhao
authors.initials: WZ
authors.lastname: Zhong
authors.affiliation: Southern Medical University, Guangzhou, 510515, China.|Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.|Medical Research Center, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Southern Medical University, Guangzhou, 510515, China.|Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Jin-Ji
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D015331:Cohort Studies; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: anaplastic lymphoma kinase (ALK); cohort study; epidermal growth factor receptor (EGFR); non-small-cell lung cancer (NSCLC); overall survival