The combination of bevacizumab (B) and erlotinib (E) shows significant biological activity in patients with advanced hepatocellular carcinoma (HCC)

4567 Purpose: HCC is the 5 th most common solid tumor worldwide and the incidence is rising in western countries. >75% of patients (pts) have advanced disease and are ineligible for surgical or loco-regional therapies. Existing cytotoxic chemotherapy does not prolong pt survival and can have significant toxicity in cirrhotic pts. HCC are highly vascular tumors, and based on the prevalence of vascular endothelial growth factor (VEGF) and epidermal growth factor receptors (EGFR) in HCC, we are conducting a phase II, single-arm, open-label trial of B and E in pts with HCC. Patients and Methods: Eligibility criteria include biopsy-proven unresectable HCC, Child- Pugh class A or B cirrhosis, bilirubin = 2.0 mg/dL, transaminases (TA)= 5 x ULN, Plts = 50,000 K/UL and ECOG PS = 2. Prior allowed therapies are surgery, external radiotherapy, ablation, chemoembolization (TACE) and one systemic therapy. Pts receive B 10 mg/kg q14 days plus E 150 mg orally daily until PD or unacceptable toxicity. Results: The primary endpoint is the percent of pts alive and progression free (PFS) after 16 wks of therapy based on median PFS of 3–5 mos in published studies. Response is evaluated by RECIST. 29 pts have been enrolled. For all pts, the med. age was 61 (29–77), 24 (82.8%) were male, 19 (65.5%) were Caucasian; ECOG PS 0, 11 pts, PS 1, 18 pts; 6 had prior systemic therapy, and 10 pts had prior TACE. Of the 27 pts evaluable for response, 1 pt confirmed CR, 5 pts PRs (4 confirmed) (22% RR; 5/6 pts 1 st line) 9 pts SD at 16 wks (55% PFS 16 wks); 5 additional pts SD at 8 wks (74% disease control rate). 2 pts PD at 16 wks, 1 pt PD at 8 wks, 2 removed for toxicity (proteinuria, fatigue); 1 early death. 12/14 pts with SD as their best response showed minor tumor shrinkage, decreased tumor vascularity or increased necrosis. Generally B+E are well tolerated; Gr 3–4 toxicities were TA elevation, hyperkalemia, acne (1 pt each), diarrhea, proteinuria (2 pts), GI bleed (3 pts), fatigue (4 pts), hypertension (5 pts). Conclusions: Based on these early encouraging results and favorable toxicity profile, the combination of B + E appears to have significant clinically meaningful biologic activity in HCC. The trial will continue to full accrual of 40 patients. The combination of B + E warrants further study in HCC. No significant financial relationships to disclose.