Bevacizumab (BVZ) as second-line treatment after sorafenib (SFB) progression in patients (pts) with advanced hepatocellular carcinoma (HCC).

e14619 Background: Single agent SFB, a multikinase inhibitor, is the only standard systemic therapy for advanced HCC that has demonstrated a survival benefit. Data are lacking for second-line treatment post-sorafenib. BVZ, a VEGF inhibitor, has proved activity against HCC in several phase II trials. The aim of this pilot study is to assess the efficacy and safety of BVZ in HCC pts when SFB therapy fails. Methods: Advanced unresectable HCC pts, progressing both clinically and radiologically on SFB treatment, were enrolled to receive BVZ at 10 mg/Kg iv every 14 days. Additional inclusion criteria were no history of myocardial infarction, stroke, thromboenbolic event or variceal bleeding within the prior 12 months (mo). Safety wass assessed throughout the study. Efficacy endpoints were time to symptomatic progression (TTSP), time to progression (TTP) and overall survival (OS). Results: 12 pts were included. Baseline characteristics: male/female: 8/4; median age 66 (range 46-87); ECOG 0/1/2: 1/1/10 (80% ECOG 2); Child Pugh A/B: 5/7 (60% Child B); etiology of underlying chronic liver disease HBV/HCV/other: 4/3/5; esophageal varices grade 1/2/3/4: 8/3/1/0 (90% grade 1-2). Tumor characteristics: BCLC stage C: 12; vascular invasion: 1; brain metastasis: 1; lung metastasis: 5; previous treatment TACE/chemotherapy/SFB: 1/1/12; previous response to SFB PD/SD/PR/CR: 6/6/0/0 (50% of pts were primary resistant to SFB therapy); basal AFP levels: range 30-57,123. Median number of BVZ cycles: 6 (range 2-26). Treatment was well tolerated with less than 15% of grade 1-2 toxicities, such as hyperbilirrubinemia, fatigue, leucopenia and plaquetopenia and one case of grade 3 toxicity consisting in esophageal bleeding in the only pt included with grade 3 esophageal varices. Radiologic response to BVZ: PD/PR/SD: 6/2/4 (50% clinical benefit). With a median follow-up of 12 mo, median TTSP was 3.8 mo (range 1.1-13.2), TTP 3.9 mo (range 1.4-14.2) and OS 9.5 mo (range 3.1-23.0). Conclusions: BVZ was active and safe as second- line treatment in poor prognosis advanced HCC pts progressing to first-line SFB therapy. Remarkably in this series a subset of HCC pts primary resistant to SFB responded to BVZ. No significant financial relationships to disclose.