Abstract
In REFLECT, lenvatinib demonstrated an effect on overall survival (OS) by confirmation of noninferiority to sorafenib in unresectable hepatocellular carcinoma. This analysis assessed correlations between serum or tissue biomarkers and efficacy outcomes from REFLECT. Serum biomarkers (VEGF, ANG2, FGF19, FGF21, and FGF23) were measured by ELISA. Gene expression in tumor tissues was measured by the nCounter PanCancer Pathways Panel. Pharmacodynamic changes in serum biomarker levels from baseline, and associations of clinical outcomes with baseline biomarker levels, were evaluated. Four hundred and seven patients were included in the serum analysis set (lenvatinib n = 279, sorafenib n = 128); 58 patients were included in the gene-expression analysis set (lenvatinib n = 34, sorafenib n = 24). Both treatments were associated with increases in VEGF; only lenvatinib was associated with increases in FGF19 and FGF23 at all time points. Lenvatinib-treated responders had greater increases in FGF19 and FGF23 versus nonresponders at cycle 4, day 1 (FGF19: 55.2% vs. 18.3%, P = 0.014; FGF23: 48.4% vs. 16.4%, P = 0.0022, respectively). Higher baseline VEGF, ANG2, and FGF21 correlated with shorter OS in both treatment groups. OS was longer for l...Continue Reading
References
Aug 20, 2002·Genome Biology·Sandrine Dudoit, Jane Fridlyand
Oct 19, 2007·International Journal of Cancer. Journal International Du Cancer·Junji MatsuiMakoto Asada
Sep 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Junji MatsuiMakoto Asada
Sep 30, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Josep M Llovet, Jordi Bruix
Dec 9, 2008·FEBS Letters·Junming YieJing Xu
Aug 12, 2009·Hepatology International·Yun-Fan LiawUNKNOWN Chronic Hepatitis B Guideline Working Party of the Asian-Pacific Association for the Study of the Liver
Aug 24, 2010·Cell and Tissue Research·Nobuyuki Itoh
Mar 15, 2011·Cancer Cell·Eric T SaweyScott Powers
Oct 7, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kevin B KimJohn M Kirkwood
Mar 1, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Josep M LlovetUNKNOWN SHARP Investigators Study Group
Feb 13, 2013·Cancer Imaging : the Official Publication of the International Cancer Imaging Society·Tiffany Hennedige, Sudhakar Kundapur Venkatesh
Aug 8, 2013·PloS One·Xing Xian YuSanjay Bhanot
Sep 10, 2014·Vascular Cell·Yuji YamamotoAkihiko Tsuruoka
Oct 9, 2014·Journal of Thyroid Research·Osamu TohyamaYasuhiro Funahashi
Jan 16, 2015·ACS Medicinal Chemistry Letters·Kiyoshi OkamotoJunji Matsui
Jun 2, 2016·International Journal of Molecular Medicine·Masaru Katoh
Jul 8, 2016·Liver Cancer·Li-Chun LuAnn-Lii Cheng
Feb 13, 2018·Lancet·Masatoshi KudoAnn-Lii Cheng
May 8, 2018·Cancer Medicine·Masahiro MatsukiJunji Matsui
Oct 3, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael A MorseRichard S Finn
Nov 18, 2018·Cancer Science·Takayuki KimuraKenichi Nomoto
Feb 1, 2019·Oncotarget·Roberto Carmagnani PestanaAhmed Kaseb
Feb 28, 2019·World Journal of Gastroenterology : WJG·Masatoshi Kudo
Apr 5, 2019·Biochemical and Biophysical Research Communications·Taisuke HoshiYasuhiro Funahashi
Apr 23, 2019·Cancer Investigation·Yusuke AdachiKenichi Nomoto
Jun 7, 2019·Cells·Aroosha RajaSung-Min Ahn
Jan 30, 2020·Cancers·Makoto ChumaShin Maeda
May 14, 2020·The New England Journal of Medicine·Richard S FinnUNKNOWN IMbrave150 Investigators
Jul 28, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Richard S FinnJosep M Llovet
Oct 27, 2020·JGH Open : an Open Access Journal of Gastroenterology and Hepatology·Taku ShigesawaNaoya Sakamoto