A phase II trial of second-line axitinib following prior antiangiogenic therapy in advanced hepatocellular carcinoma (HCC).

314 Background: Second-line options in treatment of HCC are limited. Axitinib is a multi-targeted tyrosine kinase inhibitor (TKI) of VEGFRs 1, 2, and 3, PDGFR and c-KIT that warrants exploration in HCC. Methods: This is an open-label, single-arm, two-stage phase II trial of axitinib in advanced HCC. Eligible patients (pts) are Child-Pugh A/B7, with measurable progressive disease after TKIs/antiangiogenic drugs. Axitinib starts at 5 mg bid orally, titrated to 10 mg bid as tolerated. Treatment continues to progression (PD) or intolerable toxicity. Primary endpoint is response defined by reduction in size by RECIST 1.1 on CT scan at 16 wks, secondary endpoints to compare response by RECIST 1.1 to Choi criteria and modified RECIST, explore dynamic imaging models, feasibility, safety, PFS and overall survival. Results: We present results of 15 (of 29) pts enrolled from 01/11 - 09/12. Median age; 62y (range 18-78) with ECOG PS 0 (5 pts), 1 (10 pts) with prior therapy of Temsirolimus/Bevacizumab (2 pts), sorafenib (13 pts). A planned safety/futility interim analysis was passed. Most common axitinib-related AEs were hypertension (HTN) (60%), hand-foot skin reaction (HFSR) (60%), diarrhea (60%), fatigue (50%). Most common axitinib-related grade 3 (G3) AEs were HTN (20%) and diarrhea (20%). There were no G3 HFSR. There was 1 G4 hyperbilirubinaemia. 60% of pts had dose interruptions due to AEs; most common reasons included fatigue (20%), HTN (10%), and HFSR (10%). 20% required dose reductions, 14% of pts tolerated dose escalation above 5 mg bid. As of 09/12, 8 pts remain on study, 7 pts discontinued (4pts: PD, 3pts: AEs). Med duration of treatment; 4.0 mo (range 6 d - 15.5 mo). Out of 9 evaluable for response, there was 1 confirmed PR per RECIST 1.1; 3 other pts had tumor reduction; 10%, 22%, 23%, 2 PR by Choi criteria and none by modified RECIST. Early on-treatment perfusion changes were noted on functional imaging. Of the 9 pts with evaluable AFP response, 3 (33%) had >50% decrease from baseline. 11 pts are still alive, 4 pts are deceased secondary to PD. Conclusions: Axitinib is tolerated and has shown preliminary efficacy in this VEGF pretreated HCC pt population.This is early analysis and updated data will be presented. Clinical trial information: NCT01334112.