A Phase II Trial of Second-Line Axitinib Following Prior Antiangiogenic Therapy in Advanced Hepatocellular Carcinoma

作者：McNamara Mairead G; Le Lisa W; Horgan Anne M; Aspinall Alex; Burak Kelly W; Dhani Neesha; Chen Eric; Sinaei Mehrdad; Lo Glen; Kim Tae Kyoung; Rogalla Patrik; Bathe Oliver F; Knox Jennifer J^*

来源：Cancer, 2015, 121(10): 1620-1627.

DOI：10.1002/cncr.29227

• axitinib
• second-line treatment
• HCC
• prior antiangiogenic therapy
• phase II trial

BACKGROUNDSecond-line treatment options in advanced hepatocellular carcinoma (HCC) are limited. Axitinib, a selective potent tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor VEGF) receptors 1, 2, and 3, merits exploration in HCC.
METHODSThis was a single-arm phase II trial of axitinib in advanced HCC. Eligible patients were Child-Pugh A/B7, with measurable progressive disease after TKIs/antiangiogenic drugs. Axitinib was started at 5 mg twice daily orally, titrated from 2 to 10 mg twice daily as tolerated. The primary end point was tumor control at 16 weeks by RECIST1.1; secondary end points were response rate, comparing response by RECIST1.1 to Choi and modified RECIST, exploring dynamic contrast-enhanced imaging models, safety, progression-free (PFS), and overall survival (OS).
RESULTSThirty patients were treated. Of 26 patients evaluable for response, there were 3 partial responses (PR) per RECIST1.1; 13 PR by Choi, 6 PR and 1 complete response by modified RECIST. Tumor control rate at 16 weeks was 42.3%. Two-week perfusion changes were noted on functional imaging. Of 21 patients with evaluable -fetoprotein response, 43% had >50% decrease from baseline. Most common axitinib-related grade 3/4 adverse events (AEs) were hypertension, thrombocytopenia and diarrhea. Of 11 patients with any grade hypertension, 7 had disease control >36wks. Four patients discontinued treatment due to AEs. Median PFS was 3.6months. Median OS was 7.1months.
CONCLUSIONSWith 42.3% tumor control at 16weeks, primary endpoint was met. Axitinib has shown encouraging tolerable clinical activity in VEGF-pretreated HCC patients but further study should be in a selected population incorporating potential biomarkers of response. Cancer 2015;121:1620-1627. (c) 2015 American Cancer Society.
With second-line axitinib treatment, tumor control was established in 42.3% at 16 weeks. Axitinib showed encouraging tolerable clinical activity in vascular endothelial growth factor-pretreated hepatocellular carcinoma patients, but further study is indicated in a selected population incorporating potential biomarkers of response.

• 出版日期2015-5-15