De novo pulmonary small cell carcinomas and large cell neuroendocrine carcinomas harboring EGFR mutations: Lack of response to EGFR inhibitors

Le, XiuningDeSai, NeelamMajid, AdnanKarp, RebeccaHuberman, Mark S.Rangachari, DeepaKent, MichaelGangadharan, SidhuFolch, ErikVanderlaan, PaulCosta, Daniel2018-05-252015Le, Xiuning, Neelam V. Desai, Adnan Majid, Rebecca S. Karp, Mark S. Huberman, Deepa Rangachari, Michael S. Kent, et al. 2015. “De Novo Pulmonary Small Cell Carcinomas and Large Cell Neuroendocrine Carcinomas Harboring EGFR Mutations: Lack of Response to EGFR Inhibitors.” Lung Cancer 88 (1) (April): 70–73. doi:10.1016/j.lungcan.2015.02.003.0169-5002http://nrs.harvard.edu/urn-3:HUL.InstRepos:37047104Introduction Epidermal growth factor receptor (EGFR) mutations are present in 10-20% of all non-small-cell lung cancers and predict for response to EGFR tyrosine kinase inhibitors (TKIs). However, the incidence of these mutations and their ability to predict response to TKIs in high-grade pulmonary neuroendocrine carcinomas [i.e. small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC)] is unknown. Methods The presence of EGFR mutations, clinicopathologic and anti-cancer therapy response data were retrospectively compiled and analyzed from a cohort of 608 patients-lung tumors to identify EGFR mutated high-grade pulmonary neuroendocrine carcinomas. We identified 126 EGFR-mutated (21.8% of 578 successful genotyped cases) lung cancers and only 2 (1.6%) were high-grade neuroendocrine carcinomas. Results Case one was of a 63 year-old white never smoker woman with extensive stage SCLC harboring EGFR-delL747_P753insS but without EGFR protein expression. After progression on carboplatin/etoposide, the patient was treated with erlotinib and developed progressive disease with a survival <3 months from start of erlotinib. Case two was of a 73 year-old Asian 30 pack-year smoker man with metastatic LCNEC harboring EGFR-delL747_P753insQS and also lacking EGFR protein expression. The patient received first line therapy with erlotinib and had progressive disease with a survival of 4 months. Conclusions The lack of response to EGFR TKIs in EGFR mutated de novo SCLC and LCNEC reported here may indicate that tumor differentiation affects tumor dependency on EGFR as a driver oncogene.en-USDe novo pulmonary small cell carcinomas and large cell neuroendocrine carcinomas harboring EGFR mutations: Lack of response to EGFR inhibitorsJournal Article2017-07-1320152018-05-2510.1016/j.lungcan.2015.02.003