Abstract 5736: Clinical impact of high serum hepatocyte growth factor in advanced non-small cell lung cancer

Abstract

Abstract Activation of c-MET through hepatocyte growth factor (HGF) increases tumorigenesis, induces resistance, and is associated with poor prognosis in various solid tumors. We previously reported that lung cancer cell lines had increased expression of c-MET due to gene amplification-induced cytotoxic drug resistance, and that resistant cells paracrine HGF and promote its resistance. However, the clinical significance of sHGF in patients with advanced or recurrent NSCLC, especially in patients treated with cytotoxic chemotherapy, is yet to be identified. Here, we present sHGF may be useful to predict tumor response and PFS in patients with advanced NSCLC. A total of 81 patients with 101 treatment regimens were investigated; 53 patients received first-line therapy and 48 patients received second-line therapy during the observation period. sHGF levels were evaluated using ELISA at 4 time-points: at pre-treatment, at response-evaluation (1-2 months after treatment initiation), at the best tumor response, and at the disease progression. As a control biomarker, serum carcinoembryonic antigen (CEA) was also evaluated. sHGF at response-evaluation in patients with progressive disease was higher compared with that of disease controls in both first-line and second-line treatment (median value (MV): under the limited of detection (LOD) vs. 0.40; P=0.0086 and MV: under the LOD vs. 0.41; P=0.0035, respectively). Positive-sHGF at response-evaluation predicts poor progression-free survival (PFS) compared with negative-sHGF in both first-line (median, 153.5 vs. 288.0; P=0.047) and second-line treatment (87.0 vs. 219.5; P=0.014). Lung adenocarcinoma subgroup analysis showed that in patients receiving second cytotoxic chemotherapy, there were no significant differences in PFS or HR between patients with low-CEA compared with those with high-CEA, but positive-sHGF at pre-treatment or at response-evaluation predicts poor PFS (35 vs. 132; P=0.0045, 50 vs. 215; P=0.0047, respectively). Simple and repeatable markers for activation of the HGF/c-MET pathway would provide rationale for future research investigating the merit of sHGF as a potential clinical biomarker to indicate administration of MET inhibitors. Citation Format: Takahiro Tsuji, Hiroaki Ozasa, Yuichi Sakamori, Takashi Nomizo, Tomoko Funazo, Yuto Yasuda, Hironori Yoshida, Hiroki Nagai, Young Hak Kim. Clinical impact of high serum hepatocyte growth factor in advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5736. doi:10.1158/1538-7445.AM2017-5736