A phase II open-label study of OSI-774 (NSC 718781) in unresectable hepatocellular carcinoma

Abstract

4038 Background: Hepatocellular carcinoma (HCC) is the 4th most common cancer worldwide and is increasing in the United States and other western countries. HCC are chemotherapy-resistant tumors, and current systemic therapy has been unable to prolong survival. Epidermal growth factor receptor (EGFR) is overexpressed in a majority of HCC, thus it is rational to study OSI-774, a small molecule EGFR tyrosine kinase inhibitor, in this disease. Patients and Methods: Prospective Phase II study of OSI-774 in pts with previously untreated advanced HCC. A total of 25 patients (pts) have been enrolled to date. Patients accrue to 1 of 2 strata based on low (0–2+; 6 pts, 24%) or high (3–4+; 19 pts, 76%) tumor EGFR expression by immunohistochemistry (IHC). The primary endpoint is the rate of progression-free survival at 16 weeks of OSI-774 treatment. All patients received OSI-774 at 150 mg/po daily. Demographics: male 19, female 6, median age 66, cirrhosis 12 pts, no cirrhosis 13 pts, Childs-Pugh class A, 25 pts (100%); ECOG 0, 8 pts (32%); 1, 14 pts (56%); 2, 3 pts (12%); risk factors hepatitis C virus (HCV) 9 (36%), HBV 4 pts; other 12 (48%). Functional computed tomography (fCT) scans were performed on all pts at baseline, 4, 12, and 16 wks, to evaluate whether OSI-774 changed tumor blood flow. Results: 8 pts have met the study endpoint (8/25, 32%; 1 PR); 5 high EGFR (5/19, 26.3%), 3 low EGFR (3/6, 50%); 1 pt remained on study drug for 16 months. Toxicity: Grade (Gr)1–2: 23 pts; Gr 3: 7 pts. (abdominal pain, anemia, increased bilirubin and AST, skin infection, vomiting, diarrhea). No pts required dose reduction or removal from study for drug-related toxicity. 21 pts had Gr 1–2 skin rash. All responding pts developed Gr 1(5 pts, 62.5%) or Gr 2 (3 pts, 37.5%) skin rash. Median time to progression (TTP) for all pts: 9.1 wks; median TTP for responding pts: 26.3 wks. Median survival (MS) all pts: 25 wks; MS for responding pts: 44 wks. fCT analysis appears to indicate mixed response of tumor blood flow to OSI-774. Conclusions: OSI-774 is well tolerated in pts with HCC, and provides prolonged stable disease and apparently has the potential to improve survival. Accrual will continue to 40 pts total in each strata. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech NCI