A pilot study of IV bevacizumab in hepatocellular cancer patients undergoing chemoembolization

4138 Background: Transarterial chemoembolization (TACE) provides a modest survival benefit in carefully selected patients with hepatocellular cancer (HCC) Llovet JM et al, Hepatology 37:429–42, 2003. After TACE, plasma VEGF levels rise, contributing to neovascularization (NVASC) and tumor re-growth. IV bevacizumab (BV) may inhibit NVASC, thereby improving TACE results. Methods: This pilot study evaluates NVASC using serial angiography in 30 HCC patients undergoing TACE who are randomized to either BV (10 mg/kg IV q 14 days) or observation (OBS), with cross-over to BV allowed after week 14. Angiograms are performed at day 8, week 10, and week 14. TACE is performed at day 8, and at week 14 if indicated. Eligibility criteria include platelets ≥ 60K, transaminases ≤ 5 times upper limit of normal, bilirubin ≤ 2.5 mg/dL, and Child’s class A/B disease. Results: 7 of 10 randomized patients are evaluable (5 BV, 2 OBS). After the first TACE, 1 BV patient had NVASC, but the new vessels did not supply tumor. 2 BV patients required TACE at week 14: one had recannalization, and another had pre-existing vessels not treated at day 8. 1 OBS patient required TACE at week 14 for recannalization and NVASC: he subsequently received BV. 6 patients (5 BV, 1 cross-over) have received BV for a median of 6 months, including 1 patient who remains on BV at 1 year. All patients have experienced transient grade 2 to 4 transaminitis after TACE. BV-related toxicities have included controllable grade 3 hypertension in 3 patients, and transient grade 2 proteinuria in 2 patients. One BV patient with a prior history of varices experienced a grade 3 variceal bleed within 1 week after withdrawing from study. Accrual continues, and analysis of serum angiogenic factors pre- and post-TACE is pending. Conclusions: BV is well tolerated in selected HCC patients undergoing TACE, and prolonged disease control has been achieved in the patients treated to date. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech