Title: Abstract No. 140: Phase II trial of bevacizumab combined with transarterial chemoembolization (TACE) for hepatocellular carcinoma: Initial experience at two institutions
Abstract: This phase II study was performed to evaluate tumor response and safety of concurrent bevacizumab and transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). Evidence of increased vascular endothelial growth factor activity in patients with HCC, and evidence that TACE stimulates angiogenic activity, led us to hypothesize that efficacy of TACE would be enhanced if given concurrently with an antiangiogenic agent. Patients seen with unresectable HCC were sequentially invited to participate. Those with ECOG 0-2, Childs-Pugh stage A-B, BCLC A-C were enrolled (to date, 26 patients including 21 males; mean age 64 yrs; ECOG 0-1 (n=25); Child's A (n=20)). Therapeutic protocol was bevacizumab (Genentech, CA) 10 mg/kg every two weeks (half life 20 days), TACE week three, in a 6-week cycle. Primary endpoint was tumor response, assessed by MR imaging at baseline, and 3 weeks post TACE, using size (RECIST), and contrast-enhancement (EASL). Secondary endpoints included safety (CTCAE, V 3.0) and survival. P-values calculated with t-tests. Median follow-up was 6 months (range 1.4-34). Patients received <1- 3 cycles of TACE with bevacizumab. On follow-up, evaluable index lesions (n=23) decreased from 5.9cm to 5.2cm (p<0.0005). By RECIST, 8/23 (35%) achieved partial response, 15/23 (65%) had stable disease. Targeted tumors decreased in contrast enhancement from 91% to 28% (p<0.0005). By EASL criteria, 14/23 (60%) had complete or partial response, and 9/23 (40%) had stable disease. Disease control rate was 100% by both criteria while undergoing treatment. Median overall survival was 13.5 months (n=10 censored 8/09). 15/26 (58%) patients experienced grade 3/4 toxicities possibly related to either therapy. Ten (38%) patient's toxicities resolved. The thirty day mortality rate was 4%. Concurrent TACE and bevacizumab is reasonably well tolerated in unresectable HCC patients, with 100% disease control rate by imaging criteria and 13.5 months median overall survival. Small sample size is a limitation. The results support the concept of TACE with a concurrent anti-angiogenic agent.