Hepatic arterial infusion chemotherapy followed by sorafenib in patients with advanced hepatocellular carcinoma (HICS 55): an open label, non-comparative, phase II trial

Masahiro Hatooka,Tomokazu Kawaoka,Hirotaka Kohno,Eisuke Murakami,Masaki Kitajima ,Masataka Tsuge,Hiroshi Kohno,Yoshiiku Kawakami,Yoshio Katamura,Akira Hiramatsu,Kei Morio,Hajime Amano,Yuki Inagaki,Toru Tamura,Kazuo Awai,Yuko Nagaoki,Takuya Moriya ,Takashi Nakahara,Koji Waki,Kazuaki Chayama

doi:10.1186/s12885-018-4519-y

Abstract

BackgroundIn patients with advanced hepatocellular carcinoma (HCC), evidence is unclear as to whether hepatic arterial infusion chemotherapy (HAIC) or sorafenib is superior. We performed a prospective, open-label, non-comparative phase II study to assess survival with HAIC or HAIC converted to sorafenib.MethodsFifty-five patients were prospectively enrolled. Patients received HAIC as a second course if they had complete response, partial response, or stable disease (SD) with an alpha fetoprotein (AFP) ratio < 1 or a des-γ-carboxy prothrombin (DCP) ratio < 1. Patients were switched to sorafenib if they had SD with an AFP ratio > 1 and a DCP ratio > 1 or disease progression. The primary endpoint was the 1-year survival rate. Secondary endpoints were the 2-year survival rate, HAIC response, survival rate among HAIC responders, progression-free survival, and adverse events.ResultsOf the 55 patients in the intent-to-treat population, the 1-year and 2-year survival rates were 64.0 and 48.3%, respectively. After the first course of HAIC, one (1.8%) patient showed complete response, 13 (23.6%) showed partial response, 30 (54.5%) had SD, and 10 (18.1%) patients had progressive disease. Twenty-three patients (41.8%) had SD with AFP ratios < 1 or DCP ratios < 1, and 7 (12.7%) had SD with AFP ratios > 1 and DCP ratios > 1. Thirty-seven patients (68.5%) were responders and 17 (30.9%) were non-responders to HAIC. In responders, the 1-year and 2-year survival rates were 78 and 62%, respectively.ConclusionGiven the results of this study, this protocol deserves consideration for patients with advanced HCC. This trial was registered prospectively from December 12. 2012 to September 1. 2016.

Highlights

In patients with advanced hepatocellular carcinoma (HCC), evidence is unclear as to whether hepatic arterial infusion chemotherapy (HAIC) or sorafenib is superior
We reported that among patients determined to have stable disease (SD) based on the imaging response to the first course of HAIC, those with alpha fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) ratios > 1 had significantly poorer survival times [20].That is, patients in whom AFP or DCP levels decreased had better prognoses than those in whom AFP
Study design The phase II HICS study (Hepatic Arterial Infusion Chemotherapy followed by Sorafenib) was a single-arm, prospective, open-label trial

Summary

Introduction

In patients with advanced hepatocellular carcinoma (HCC), evidence is unclear as to whether hepatic arterial infusion chemotherapy (HAIC) or sorafenib is superior. New treatment modalities have been developed, including surgical resection, radiofrequency ablation [3], percutaneous ethanol injection, transcatheter arterial chemoembolization (TACE), and hepatic arterial infusion chemotherapy (HAIC), resulting in improved prognosis in HCC patients [4,5,6,7,8,9,10,11,12]. Two phase III clinical trials of sorafenib for advanced HCC showed significant efficacy in terms of overall survival (OS) time compared with placebo [13, 14]. Based on these studies, sorafenib has become the standard of therapy for advanced HCC. The survival advantage of sorafenib has been described as insufficient

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Conclusion