• Yoshifumi Matsumoto, Makoto Maemondo, Yoshiki Ishii, Koichi Okudera, Yoshiki Demura, Kei Takamura, Kunihiko Kobayashi, Naoto Morikawa, Akihiko Gemma, Osamu Ishimoto, Kazuhiro Usui, Masao Harada, Satoru Miura, Yuka Fujita, Ikuro Sato, Yasuo Saijo, and North-East Japan Study Group.
• Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
• Lung Cancer. 2014 Nov 1; 86 (2): 195-200.

ObjectivesEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are particularly effective in non-small cell lung cancer (NSCLC) patients harboring active EGFR mutations. However, some studies have reported survival benefits in NSCLC patients with wild-type EGFR upon erlotinib treatment. This trial was conducted to evaluate the efficacy of erlotinib monotherapy and investigate the predictive values of several biomarkers.Patients And MethodsPatients with previously treated NSCLC but without EGFR gene mutations that had never or light smoked were eligible for this study. Gene status screening was performed using the PNA-LNA PCR clamp method. Erlotinib was administered until disease progression or unacceptable toxicities occurred. EGFR gene status was re-evaluated using the fragment method to detect exon 19 deletions and the Cycleave-PCR method to detect point mutations. Expression of hepatocyte growth factor (HGF), Met, and thymidylate synthase (TS) were evaluated using immunohistochemistry.ResultsForty-seven patients were enrolled in the study between March 2010 and November 2011. Objective response rate (ORR) and disease control rate (DCR) were 15.2% and 41.3%. Re-evaluations for EGFR gene were performed in 32 tumor samples. EGFR gene mutations were found in eight samples (5:exon 19 deletion, 2:G719X, 1:L858R). Six patients had PR and two had SD among these eight patients. A total of 24 patients were confirmed as wild-type EGFR using different methods. ORR and DCR were 4.2% and 41.7%. The median progression free survival (PFS) and median survival times were 2.0 and 6.0 months, respectively. Patients with tumors expressing HGF showed shorter PFS but not MET or TS.ConclusionsRe-examination of EGFR gene status using different detecting method or different sample should be considered to grasp a chance of erlotinib treatment after first line treatment. In confirmed EGFR wild NSCLC, negative HGF staining could be a biomarker for longer PFS by erlotonib treatment.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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