Activity of EGFR-tyrosine kinase and ALK inhibitors for EML4–ALK-rearranged non–small–cell lung cancer harbored coexisting EGFRmutation

Akihiko Miyanaga, Kumi Shimizu, Rintaro Noro, Masahiro Seike, Kazuhiro Kitamura, Seiji Kosaihira, Yuji Minegishi, Takehito Shukuya, Akinobu Yoshimura, Masashi Kawamoto, Shinichi Tsuchiya, Koichi Hagiwara, Manabu Soda, Kengo Takeuchi, Nobuyuki Yamamoto, Hiroyuki Mano, Yuichi Ishikawa, Akihiko Gemma

The EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) fusion oncogene represents a novel molecular target in a small subset of non-small-cell lung cancers (NSCLCs). The EML4-ALK fusion gene occurs generally in NSCLC without mutations in epidermal growth factor receptor (EGFR) and KRAS. We report that a case of EML4-ALK-positive NSCLC with EGFR mutation had a response of stable disease to both an EGFR tyrosine kinase inhibitor (EGFR-TKI) and ALK inhibitor. We described the first clinical report of a patient with EML4-ALK-positive NSCLC with EGFR mutation that had a response of stable disease to both single-agent EGFR-TKI and ALK inhibitor. EML4-ALK translocation may be associated with resistance to EGFR-TKI, and EGFR signaling may contribute to resistance to ALK inhibitor in EML4-ALK-positive NSCLC.