• Jin-Ji Yang, Xu-Chao Zhang, Jian Su, Chong-Rui Xu, Qing Zhou, Hong-Xia Tian, Zhi Xie, Hua-Jun Chen, Yi-Sheng Huang, Ben-Yuan Jiang, Zhen Wang, Bin-Chao Wang, Xue-Ning Yang, Wen-Zhao Zhong, Qiang Nie, Ri-Qiang Liao, Tony S Mok, and Yi-Long Wu.
• Authors' Affiliations: Division of Pulmonary Oncology, Cancer Center, Guangdong Lung Cancer Institute; Medical Research Center, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou; and State Key Laboratory of Southern China, The Chinese University of Hong Kong, Sir YK Pau Cancer Center, Prince of Wales Hospital, Hong Kong, China.
• Clin Cancer Res. 2014 Mar 1; 20 (5): 1383-92.

PurposeWe investigated the incidence of concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements in Chinese patients with non-small cell lung cancer (NSCLC), and assessed responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib in such tumors.Experimental DesignWe screened 977 consecutive patients with NSCLC for the presence of concomitant EGFR mutations and ALK rearrangements by rapid amplification of cDNA ends-coupled PCR sequencing and FISH. Immunohistochemistry (IHC) and Western blotting were used to correlate the activation of EGFR, ALK, and downstream proteins with responses to EGFR-TKIs and crizotinib.ResultsThe overall frequency of concomitant EGFR mutations and ALK rearrangements was 1.3% (13/977). EGFR/ALK co-alterations were found in 3.9% (13/336) EGFR-mutant and 18.6% (13/70) ALK-rearranged patients. Ten tumors were treated with first-line EGFR-TKIs, with a response rate of 80% (8/10). Two tumors with high phospho-ALK levels and low phospho-EGFR levels achieved stable and progressive disease, respectively. Median progression-free survival was 11.2 months. Coexpression of mutant EGFR and ALK fusion proteins in the same tumor cell populations was detected by IHC. Two cases with high phospho-ALK levels treated with crizotinib achieved partial responses; two cases with low phospho-ALK levels had progressive or stable disease.ConclusionALK rearrangements and EGFR mutations could coexist in a small subgroup of NSCLC. Advanced pulmonary adenocarcinomas with such co-alterations could have diverse responses to EGFR-TKIs and crizotinib. Relative phospho-ALK and phospho-EGFR levels could predict the efficacy of EGFR-TKI and crizotinib.©2014 AACR

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