Hepatic arterial infusion chemo improves OS vs TACE in large HCC

Hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin and oxaliplatin (FOLFOX) as first-line treatment significantly improves overall survival (OS) vs transarterial chemoembolization (TACE) in patients with large, unresectable hepatocellular carcinoma (HCC), a phase III trial in China has shown.

The open-label, parallel-group trial included 315 patients (median age, 53 years; male, 87.6 percent; hepatitis B virus [HBV] infection as HCC aetiology, 89 percent) with unresectable HCC with largest diameter ≥7 cm, without macrovascular invasion or extrahepatic spread, recruited from four hospitals in mainland China. The patients were randomized 1:1 to receive FOLFOX-HAIC (oxaliplatin 130 mg/m², leucovorin 400 mg/m², fluorouracil bolus 400 mg/m² on day 1, and fluorouracil infusion 2,400 mg/m² for 24 hours, Q3W) or TACE (epirubicin 50 mg, lobaplatin 50 mg, and lipiodol and polyvinyl alcohol particles). [J Clin Oncol 2021;doi:10.1200/JCO.21.00608]

OS, the trial’s primary endpoint, was of a median of 23.1 months in the FOLFOX-HAIC group vs 16.1 months in the TACE group (hazard ratio [HR], 0.58; 95 percent confidence interval [CI], 0.45 to 0.75; p<0.001). A significant OS benefit was observed with FOLFOX-HAIC in most subgroups of patients except in those with a Child-Pugh score of A (6 points) (HR, 0.81; 95 percent CI, 0.46 to 1.41) and in HBV-negative patients (HR, 0.91; 95 percent CI, 0.44 to 1.88).

Progression-free survival (PFS), a secondary endpoint, was also significantly improved with FOLFOX-HAIC vs TACE (median, 9.6 months vs 5.4 months; HR, 0.57; 95 percent CI, 0.45 to 0.72; p<0.001). A significant PFS benefit was observed with FOLFOX-HAIC in most subgroups except in females (HR, 0.85; 95 percent CI, 0.42 to 1.72), those with Child-Pugh score of A (6 points) (HR, 0.89; 95 percent CI, 0.52 to 1.52), and HBV-negative patients (HR, 0.79; 95 percent CI, 0.39 to 1.59).

Likewise, objective response rate (ORR) was significantly higher with FOLFOX-HAIC vs TACE (46 percent vs 18 percent; p<0.001), as was complete response rate (CRR; 13 percent vs 3 percent; p=0.002).

In terms of adverse events (AEs), TACE was associated with significantly higher frequencies of grade 3/4 alanine transaminase elevation (19 percent vs 8 percent; p=0.005), aspartate transaminase elevation (28 percent vs 18 percent; p=0.03), and hyperbilirubinaemia (6 percent vs 1 percent; p=0.01) vs FOLFOX-HAIC. The overall incidence of serious AEs was also significantly higher with TACE vs FOLFOX-HAIC (30 percent vs 19 percent; p=0.03).

“Particular abdominal pain was observed in 37 patients in the FOLFOX-HAIC group when oxaliplatin was injected, and the pain resolved when the injection was stopped. Among these 37 patients, 32 [86 percent] had particular abdominal pain when the tumour had shrunk significantly,” the investigators pointed out. “Notably, 25 patients [16 percent] in the FOLFOX-HAIC group had a dose reduction of oxaliplatin due to particular abdominal pain.”

“Within 30 days after the study treatment was stopped, four treatment-related deaths [two in each group] that were not attributed to disease progression were observed,” they added.

In previous studies, TACE was associated with significantly lower CRR in HCC tumours >5 cm vs smaller tumours (25 percent vs 64 percent), with an OS of only 11.2–13.2 months in patients with tumours >7 cm. [J Vasc Interv Radiol 2013;24:509-517; Hepatology 2002;35:1164-1171; J Vasc Interv Radiol 2018;29:1068-1077.e2; J Natl Cancer Inst 2013;105:59-68] TACE using drug-eluting beads or radioembolization with Yttrium-90 microspheres was not shown to provide superior OS vs conventional TACE (used as control treatment in the current study). [Cardiovasc Intervent Radiol 2010;33:41-52; Br J Cancer 2014;111:255-264; Gastroenterology 2016;151:1155-1163.e2]

“Our results show that HAIC represents an appropriate frontline locoregional intervention in selected patients with large, unresectable HCC,” the investigators suggested. “The optimal regimen for HAIC remains controversial. In HCC, oxaliplatin-based HAIC may be more effective than fluorouracil-based HAIC.” [Chin J Cancer 2017;36:83; Nat Med 2017;23:461-471; Anticancer Drugs 2004;15:647-650]