Clinical outcomes of advanced non-small-cell lung cancer patients with EGFR mutation, ALK rearrangement and EGFR/ALK co-alterations

// Na-Na Lou 1, 2, 3, * , Xu-Chao Zhang 2, 3, * , Hua-Jun Chen 2 , Qing Zhou 2 , Li-Xu Yan 4 , Zhi Xie 3 , Jian Su 3 , Zhi-Hong Chen 3 , Hai-Yan Tu 2 , Hong-Hong Yan 2 , Zhen Wang 2 , Chong-Rui Xu 2 , Ben-Yuan Jiang 2 , Bin-Chao Wang 2 , Xiao-Yan Bai 2 , Wen-Zhao Zhong 2 , Yi-Long Wu 1, 2, 3 , Jin-Ji Yang 1, 2 1 Southern Medical University, Guangzhou, 510515, China 2 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China 3 Medical Research Center, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China 4 Department of Pathology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China * These authors have contributed equally to this work Correspondence to: Jin-Ji Yang, email: yangjinji2003@163.com Yi-Long Wu, email: syylwu@live.cn Keywords: non-small-cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), overall survival, cohort study Received: May 11, 2016 Accepted: July 19, 2016 Published: August 11, 2016 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.