Gefitinib in the adjuvant treatment of hepatocellular carcinoma: A pilot study by the Singapore hepatocellular carcinoma consortium.

Abstract

TPS210 Background: The epidermal growth factor receptor (EGFR) pathway may play an important role in the pathogenesis of hepatocellular carcinoma (HCC) as it is expressed in 75% of patients' tumors in contrast to 30% of normal hepatocytes. Gefitinib, an oral tyrosine kinase inhibitor that targets the EGFR, is approved for the treatment of lung cancer in Asia. We intended to study the feasibility of gefitinib in the adjuvant treatment of patients with HCC and to identify prognostic and predictive biomarkers. Methods: We designed a multicenter pilot study. Patients with a clinical diagnosis of potentially resectable hepatocellular carcinoma who are willing to give informed consent prior to surgery and who have adequate end-organ function are eligible for screening. Patients with macroscopically resected disease (at least R1 resection or better) and pathologically confirmed hepatocellular carcinoma are eligible for adjuvant therapy. Treatment consists of gefitinib 250 mg orally daily for 6 months. Primary endpoints are to assess the feasibility of conducting a larger randomized trial and correlative studies. We aim to study selected genetic and/or protein markers as prognostic and predictive factors. These include: EGFR, p-EGFR, MEK, ARK in tumor tissues; serum insulin growth factor I/II, insulin growth factor binding protein-3, VEGF, PDGF, AFP, and PIVKAII; and hyper-methylation of tumor suppressor genes SOCS-1, GSTP, APC, p16, and p53 from the specimen at resection. Secondary endpoints are progression-free survival, toxicity and overall survival. Sample size is 40 eligible patients. Sixty-seven patients have been approached to participate. Forty-five consented and enrolled in the trial. Fifteen patients were ineligible (due to diagnosis other than HCC, 4 patients; poor post-operative recovery, 4 patients; unresectable disease, 3 patients; withdrawal of consent, 2 patients; 1 patient was diagnosed with bladder cancer and another developed metastatic disease before adjuvant treatment started). Thirty patients have started adjuvant treatment with gefitinib. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca