Efficacy and Safety of Bavituximab in Combination with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Arm, Open-Label, Phase II Clinical Trial

Background: Bavituximab, an immunomodulator, targets phosphatidylserine (PS), a membrane lipid externalized on tumor and endothelial cells in response to sorafenib. Objective: The objective of this phase II study was to assess the efficacy of combination bavituximab and sorafenib in advanced hepatocellular carcinoma (HCC). Methods: In this single-arm phase II study, patients with HCC determined to be unresectable with Eastern Cooperative Oncology Group (ECOG) score ≤ 2, Child–Pugh score A/B7 received intravenous bavituximab 3 mg/kg weekly and oral sorafenib 400 mg twice daily until disease progression or intolerable toxicity. We investigated time to progression (TTP) for patients receiving combination bavituximab and sorafenib compared with that for sorafenib-only historical controls. Results: In total, 38 patients were accrued. The median follow-up was 6.1 months. Patient characteristics were as follows: median age 61 years; male 82%; hepatitis C virus 79%; Black 39%, Hispanic 26%, White 29%; previous treatment 39%; macrovascular invasion 84%; and extrahepatic metastases 24%. The median TTP was 6.7 months (95% confidence interval [CI] 4–17). The median overall survival was 6.1 months (95% CI 5–8), and the median disease-specific survival was 8.6 months (95% CI 6–14). Two patients experienced partial responses; none had a complete response. The disease control rate was 58%. Treatment-related adverse events were observed in 63% of patients, with the most commonly reported therapy-related symptoms being diarrhea (32%), fatigue (26%), and anorexia (24%). Conclusions: The efficacy of adding bavituximab to sorafenib for the treatment of advanced HCC was inconclusive; however, the combination regimen did not exacerbate toxicities associated with single-agent sorafenib. ClinicalTrials.gov identifier: NCT01264705.