Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma

Growth factor overexpression, including epidermal growth factor receptor (EGFR) expression, is common in hepatocellular cancers. Erlotinib is a receptor tyrosine kinase inhibitor with specificity for EGFR. The primary objective of this study was to determine the proportion of hepatocellular carcinoma (HCC) patients treated with erlotinib who were alive and progression-free (PFS) at 16 weeks of continuous treatment.

Patients with unresectable HCC, no prior systemic therapy, performance status (PS) of 0, 1, or 2, and Childs-Pugh (CP) cirrhosis A or B received oral erlotinib 150 mg daily for 28-day cycles. Tumor response was assessed every 2 cycles by using Response Evaluation Criteria in Solid Tumors (RECIST; National Cancer Institute Cancer Therapy Evaluation Program, Bethesda, Md) criteria. Patients accrued to either "low" or "high" EGFR expression cohorts; each cohort had stopping rules applied when there was a lack of efficacy.

Forty HCC patients were enrolled. Median age was 64 years (range, 33-83 years), sex distribution was 32 males and 8 females, performance scores were 40% PS 0, 55% PS 1, Childs-Pugh distribution was 75% A and 20% B. There were no complete or partial responses; however, 17 of 40 patients achieved stable disease at 16 weeks of continuous therapy. The PFS at 16 weeks was 43%, and the median overall survival (OS) was 43 weeks (10.75 months). No patients required dose reductions of erlotinib. No correlation between EGFR expression and outcome was found.

Results of this study indicated that single-agent erlotinib is well tolerated and has modest disease-control benefit in HCC, manifested as modestly prolonged PFS and OS when compared with historical controls.