SERUM HGF AS PREDICTIVE FACTOR OF EGFR TKIs RESPONSE IN LUNG CANCER

NEW YORK (Reuters Health) Sep 06 - Low pretreatment serum hepatocyte growth factor (HGF) levels predict a better response to EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC), researchers from Japan report in the August 2nd Clinical Cancer Research online.

"Combined with the EGFR mutation status," the investigators conclude, "measurement of the serum HGF level might further refine the selection of patients likely to respond to EGFR-TKIs treatment, especially in the wild-type EGFR subgroup, thereby increasing the clinical benefit of EGFR-TKI treatment."

Dr. Kazuto Nishio from Kinki University School of Medicine, Osaka, and colleagues retrospectively studied the serum concentrations of 13 molecules in 95 patients with NSCLC who underwent treatment with EGFR-TKIs.

Serum concentrations of HGF and VEGF were most strongly associated with tumor response, but serum concentrations of epidermal growth factor, heparin-binding EGF-like growth factor, and tenascin C were also significantly higher among patients with progressive disease than among patients without progressive disease.

A cutoff value of 1228 pg/mL for HGF discriminated progressive disease from partial remission/stable disease with 84.8% sensitivity and 67.7% specificity, whereas a cutoff value of 1187 pg/mL for VEGF provided 78.8% sensitivity and 71.0% specificity.

In multivariate analyses that included EGFR status as a stratification factor, HGF and VEGF were both significant predictors of progression-free survival, but only HGF significantly predicted overall survival.

A high concentration of HGF predicted shorter progression-free survival and overall survival independently of EGFR status, gender, and performance status, and there wasn't any interaction between EGFR status and HGF in the final multivariate model.

"This finding indicates the possibility of using the serum HGF level to refine the indications for patients who are likely to respond to EGFR-TKIs treatment," the authors conclude. "In particular, patients with wild-type EGFR are considered to be less sensitive to EGFR-TKIs, but our results might allow the identification of a selective subgroup of these patients who might actually benefit from this treatment."

They add, "When used in combination with the EGFR mutation status, the serum HGF level might increase the clinical benefit of EGFR-TKIs by allowing the further individualization of this treatment. We plan to conduct a prospective study to validate the ability of the serum HGF level to predict the response to EGFR-TKIs treatment."

HGF, a member of the plasminogen family, has also been associated with a poor prognosis in colorectal, esophageal, gastric, and prostate cancer, as well as in malignant myeloma.

Clin Cancer Res. August 12, 2010. Abstract