A randomized phase II/III trial of three weekly cisplatin based transarterial chemoembolization (TACE) versus embolization (TAE) alone for hepatocellular cancer (HCC).

Abstract

4025 Background: TACE is regarded as the standard of care for intermediate stage HCC but evidence that TACE is superior to TAE is lacking. Methods: Eligible patients had previously untreated HCC based on histology or AASLD criteria; were unsuitable for resection; had multifocal disease or one lesion ≥ 3 cm, PS ≤ 2, Hb ≥ 9g/L, platelets ≥ 50x109/L, INR ≤ 1.5, GFR ≥ 50 mL/min, bilirubin ≤ 100 μ mol/L, and no extrahepatic disease or main branch portal vein occlusion. Patients were randomised to receive TAE with polyvinyl alcohol (PVA) particles alone or TACE in which cisplatin 50 mg was administered intrarterially 4-6 hours before PVA embolization. Treatment was repeated three weekly for a maximum of three treatments. The primary endpoint was overall survival (OS) and secondary endpoints were progression free survival (PFS), toxicity and response. Target sample size for phase II and III was 80 and 322 respectively. Results: Eighty-five patients were randomised (41 TAE, 44 TACE). Median age 62 years (range 30-80); 87% men; 81% Child-Pugh A cirrhosis; 82% PS 0/1, 64% multifocal disease. Etiology was Hep B in 16%, Hep C in 36% and alcohol in 20%. Currently 58% (TAE) and 57% (TACE) patients have received all three planned treatments. There was no significant difference in toxicity, with 24 (TAE) and 28 (TACE) patients reporting at least one grade 3/4 toxicity. Response rates according to RECIST for TAE vs. TACE were; PR 10% vs. 25%, SD 37% vs. 36%, PD 17% vs. 7% (p = 0.165). Eight vs. 9 patients subsequently had a liver transplant following treatment and were censored for survival at the date of surgery. Median PFS was 6.9 (TAE) vs 7.8 months (TACE) (p = 0.64) and median OS was 16.2 vs. 15.9 months (p = 0.82). When transplanted patients were excluded, the median survival was 14.6 vs 12.7 months (p = 0.76). Conclusions: Based on these results, the chance of seeing a survival difference of > 2 months between TACE and TAE in a phase III trial was < 20%. The trial was therefore terminated at phase II. No significant financial relationships to disclose.