title: A phase II trial of second-line axitinib following prior antiangiogenic therapy in advanced hepatocellular carcinoma.
abstract: BACKGROUND
  Second-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.
  
  
  METHODS
  This 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).
  
  
  RESULTS
  Thirty 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 α-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 >36 wks. Four patients discontinued treatment due to AEs. Median PFS was 3.6 months. Median OS was 7.1 months.
  
  
  CONCLUSIONS
  With 42.3% tumor control at 16 weeks, 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.
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; The Christie NHS Foundation Trust/University of Manchester, Withington, Manchester, United Kingdom.
authors.forename: Mairéad G
authors.initials: MG
authors.lastname: McNamara
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Le
authors.forename: Anne M
authors.initials: AM
authors.lastname: Horgan
authors.forename: Alex
authors.initials: A
authors.lastname: Aspinall
authors.forename: Kelly W
authors.initials: KW
authors.lastname: Burak
authors.forename: Neesha
authors.initials: N
authors.lastname: Dhani
authors.forename: Eric
authors.initials: E
authors.lastname: Chen
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Sinaei
authors.forename: Glen
authors.initials: G
authors.lastname: Lo
authors.forename: Tae Kyoung
authors.initials: TK
authors.lastname: Kim
authors.forename: Patrik
authors.initials: P
authors.lastname: Rogalla
authors.forename: Oliver F
authors.initials: OF
authors.lastname: Bathe
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077784:Axitinib; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012008:Recurrence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000509:alpha-Fetoproteins; D000077784:Axitinib; D011505:Protein-Tyrosine Kinases
keywords: HCC; axitinib; phase II trial; prior antiangiogenic therapy; second-line treatment