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26 January 2016 : Clinical Research  

Hepatic Metastases is Associated with Poor Efficacy of Erlotinib as 2nd/3rd Line Therapy in Patients with Lung Adenocarcinoma

Yayi HeE, Yan WangB, Theresa BoyleE, Shengxiang RenB, Dan ChanC, Chris RivardF, Xuefei LiF, Jiayu LiE, Caicun ZhouAG, Fred R. HirschF

DOI: 10.12659/MSM.896607

Med Sci Monit 2016; 22:276-283

Abstract

BACKGROUND: Hepatocyte growth factor (HGF)-mediated mesenchymal-to-epithelial transition factor (MET) gene amplification is a common mechanism for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). MET gene amplification has also been associated with hepatic metastases in patients with lung cancer. The aim of this study was to investigate whether hepatic metastases are associated with decreased efficacy of erlotinib in patients with adenocarcinoma.

MATERIAL AND METHODS: A cohort of 329 patients with stage IV lung adenocarcinoma, known EGFR mutation status, and who received treatment with erlotinib in the 2nd or 3rd line setting were enrolled into this study over a period of 4 years between January 2011 and January 2015. The cohort was stratified based on the presence or absence of hepatic metastases and the efficacy of erlotinib was defined based on disease control rate (DCR) and progression-free survival (PFS).

RESULTS: Hepatic metastases were present in 220 of the 329 enrolled lung adenocarcinoma patients. EGFR-activating mutations (exon 19 deletion or an exon 21 L858R mutation) were identified in 113 (34.3%) patients. The DCR was significantly lower in the hepatic metastases group than in patients without hepatic metastases (39.5% vs. 51.4% P=0.045). In patients with hepatic metastases, median PFS was 2.3 months in the EGFR mutation-positive group versus 1.4 months in the EGFR mutation-negative group (95% CI 1.3–3.3 vs. 1.3–1.5; P=0.055). Of note, erlotinib therapy in patients with hepatic metastases was complicated by elevated alanine transaminase (ALT) levels.

CONCLUSIONS: Hepatic metastasis in patients with lung adenocarcinoma predicts poor response to erlotinib as a 2nd/3rd line therapy. Combination therapy, for example with MET-TKI, may be a good choice for patients with liver metastases with poor prognosis.

Keywords: Adenocarcinoma - pathology, Disease-Free Survival, Erlotinib Hydrochloride - therapeutic use, Liver Neoplasms - secondary, Lung Neoplasms - pathology, Mutation - genetics, Receptor, Epidermal Growth Factor - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750