984P - Sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib alone for advanced hepatocellular carcinoma with major portal vein tumor thrombosis (Vp3/4): A randomized phase II trial

Background

The first-line treatment with sorafenib for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) shows limited survival benefit. Previous reports have suggested the application of hepatic arterial infusion chemotherapy (HAIC) for these patients. This single-centre, randomized phase II trial (NCT03009461) was conducted to investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for advanced HCC with major PVTT (Vp3/4).

Methods

Patients with unresectable advanced HCC and main (Vp3) or first branch PVTT (Vp4) who were previously untreated with chemotherapy or radiotherapy were recruited from June 2017 to November 2019. Patients were randomly assigned in a 1:1 ratio to receive sorafenib (400 mg, twice daily) plus HAIC (oxaliplatin 35 mg/m² for 2 h, and 5-fluorouracil 600 mg/m² for 22 h on days 1-3) or sorafenib (400 mg, twice daily) every four weeks. Percutaneously port catheter system was used for HAIC. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR) according to mRECIST, progression-free survival (PFS) and safety.

Results

The intention to treat population included 64 patients, 32 in sorafenib-HAIC group and 32 in sorafenib group. The median OS was 23.5 months (95%CI: 10.2-36.8) in the sorafenib-HAIC group and 6.8 months (95%CI: 4.8-8.8) in the sorafenib group (P<0.001). Higher ORR (16 [57.1%] vs. 1 [4.0%], P<0.001) and longer median PFS (10.7 [95%CI: 4.1- 17.3] vs. 2.5 [95%CI: 1.3-3.7] months, P<0.001) was observed in Sorafenib-HAIC than in sorafenib group. The most frequent Grade 3 or 4 treatment-related AEs were gastrointestinal reaction (7 [21.9%] vs. 6 [18.8%]), hand-foot syndrome (6 [18.8%] vs. 2 [6.2%]), hematological abnormalities (4 [12.5%] vs. 0) and liver dysfunction (2 [6.3%] vs. 1 [3.1%]). No treatment-related death occurred.

Conclusions

Sorafenib plus HAIC with oxaliplatin and 5-fluorouracil significantly improved survival compared with sorafenib in patients with HCC and major PVTT, with acceptable safety profile.

Clinical trial identification

NCT03009461, June 2017.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.