AOSOP3 Combination of bevacizumab and erlotinib in the treatment of patients with advanced hepatocellular carcinoma with sorafenib-refractory disease: Results of a pilot phase II study

Background The combination of bevacizumab and erlotinib has shown promising clinical outcomes as the first-line treatment for patients with advanced hepatocellular carcinoma (HCC). We aimed to assess the efficacy and safety of using the combination as a second-line treatment for patients with advanced HCC who had failed first-line sorafenib treatment. Methods Eligible patients with advanced HCC and documented radiological evidence of disease progression with sorafenib treatment were recruited. All patients received bevacizumab at 10 mg/kg every 2 weeks with erlotinib at 150 mg daily for a maximum of six cycles. Response assessments using both Response Evaluation Criteria in Solid Tumours (RECIST) and modified RECIST criteria were done after every 6 weeks. The primary end-point was the rate of clinical benefit and the major secondary end-points were response rate, time-to-progression (TTP), and overall survival (OS). Findings The trial was stopped during the first stage according to the pre-set statistical criteria with 10 patients recruited. The median age was 47 years (range 28–61) and all patients had Eastern Cooperative Oncology Group (ECOG) performance status 1. Eighty per cent of patients were chronic hepatitis B carriers and all patients had Child A cirrhosis. None of the 10 enroled patients achieved response or stable disease. The median TTP was 1.81 months (95% confidence interval [CI], 1.08–1.74) and OS was 4.37 months (95% CI, 1.08–11.66). Rash (70%), diarrhoea (50%), and malaise (40%) were the most common toxicities. Interpretation The combination of bevacizumab and erlotinib was well tolerated but had no activity in an unselected sorafenib-refractory population of patients with advanced HCC. The authors declared no conflicts of interest.