Prospective phase II trial of sorafenib combined with doxorubicin eluting bead-transarterial chemoembolization for patients with unresectable hepatocellular carcinoma: Efficacy analysis.

4124 Background: This study reports the final analysis (n=50) of a prospective phase II study evaluating the efficacy of the combination of sorafenib and doxorubicin eluting bead transarterial chemoembolization (DEB-TACE) in patients with unresectable hepatocellular carcinoma (HCC). Methods: Protocol consisted of 6-week cycles with sorafenib at 800 mg/day beginning 1 week prior to DEB-TACE; up to 4 DEB-TACE treatments within 6 months. Tumor response was assessed by RECIST and EASL criteria using MRI at baseline and at 1 month follow-up. Time to untreatable progression (TTUP) was defined as the interval from initiation of sorafenib therapy until inability of patient to further receive intra-arterial therapy. Overall survival (OS) and TTUP were calculated with the Kaplan-Meier method; outcomes were stratified by BCLC A/B and C and compared with the log-rank test. Results: DEB-TACE + sorafenib successfully performed in 50 patients: mean 62yrs (range, 31-88 yrs), Child-Pugh A/B (92%/8%), BCLC A/B/C (10%/28%/62%), ECOG 0/1 (52%/48%), HCV/HBV (44%/8%), mean tumor burden 20%, mean tumor size 7.2cm (range, 1–17.6), and mean tumor enhancement 78%. Patients were enrolled for a median of 3 (range, 1-22) cycles including a median of 1 (range, 0-6) DEB-TACE procedure. Median dose regimen was 400mgQD and the median dose taken while on study was 318 mg/day (range, 100-800). 1 month follow-up showed a mean tumor enhancement reduction of 48.2% (n=46, p<0.001) and an average reduction in lesion diameter of 8.5%(n=48, p=0.02). The Disease Control Rate was 98% using the EASL amendment and RECIST. Median TTUP was 11.9 mths (95% CI, 1.8-22 mths) with a significant difference between BCLC A/B (median 22.9 mths) and BCLC C (median 6.2mths) patients (log-rank, p=0.01). Median OS was 24.5 mths (95% CI, 14.3-35 mths) with a significant difference between BCLC C (median 17.1 mths) and BCLC A/B (median 33.7 mths) patients (log-rank, p=0.001). Conclusions: The results of this phase II study suggest a potential benefit to the combination of sorafenib and DEB-TACE. Single arm and non-randomization are limitations of the study. Clinical trial information: NCT00844883.