@article{69cdaced9ed3459c8497a3668a9f08ea,
title = "Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab",
abstract = "Background: Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2). Methods: Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed. Results: Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001). Conclusions: AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab. Clinical Trial Registration: ClinicalTrials.gov, REACH (NCT01140347) and REACH-2 (NCT02435433).",
author = "Zhu, {Andrew X.} and Finn, {Richard S.} and Kang, {Yoon Koo} and Yen, {Chia Jui} and Galle, {Peter R.} and Llovet, {Josep M.} and Eric Assenat and Giovanni Brandi and Kenta Motomura and Izumi Ohno and Bruno Daniele and Arndt Vogel and Tatsuya Yamashita and Hsu, {Chih Hung} and Guido Gerken and John Bilbruck and Yanzhi Hsu and Kun Liang and Widau, {Ryan C.} and Chunxiao Wang and Paolo Abada and Masatoshi Kudo",
note = "Funding Information: Funding information This study was sponsored by Eli Lilly and Company. Medical writing assistance was provided by John Bilbruck of ProScribe—Envision Pharma Group and was funded by Eli Lilly and Company. Funding Information: Competing interests A.X.Z. reports that his institution received research support from Eli Lilly and Company. R.S.F. reports consultant/advisory roles with AstraZeneca, Bayer, Bristol-Myers Squibb, C-Stone, Eisai, Eli Lilly, Exelixis, F. Hoffmann-La Roche, Genentech, Merck, Novartis and Pfizer. Y.-K.K. reports consultant/advisory roles with Bristol-Myers Squibb, DAE HWA Pharmaceutical, Lilly/ImClone, Merck Serono, Ono Pharmaceutical, Roche/Genentech and Taiho Pharmaceutical; and research funding from DAE HWA Pharmaceutical and LSK Biopharma. C.-J.Y. has no relationships to disclose. P.R.G. has been on advisory boards and received lecture fees from Bayer, Bristol-Myers Squibb, MSD, Merck, Sirtex, AstraZeneca, Sillajen, Eli Lilly and Company, Ipsen, Roche and Novartis. J.M.L. received grants and personal fees from Bayer, Eisai Inc., Bristol-Myers Squibb, Ipsen, Blueprint and Incyte, as well as personal fees from Eli Lilly and Company, Celsion Corporation, Exelixis, Merck, Clycotest, Navigant, Leerink Swann LLC, Midatech Ltd, Fortress Biotech Inc., Spring Bank Pharmaceuticals and Nucleix, outside the submitted work. E.A. has received honoraria from Bayer, Novartis and Sirtex Medical, and reports consultant/advisory roles with Ipsen and Sanofi. G.B. has no relationships to disclose. K.M. has received honoraria from Eisai. I.O. has had a consulting/advisory role with Merck Serono, and has been on the Speakers{\textquoteright} Bureau for Taiho Pharmaceutical. B.D. has received honoraria from Bayer, Eisai, Eli Lilly and Company, Ipsen and MSD, and reports consultant/advisory roles with AstraZeneca, Bayer, Eisai, Ipsen, MSD, Roche and Sanofi. A.V. reports consultant/advisory roles with Eli Lilly and Company, Bayer, MSD, Roche, Novartis, AstraZeneca and Beigene. T.Y. has been on the Speakers{\textquoteright} Bureau for Bayer, Eisai and Eli Lilly and Company. C.-H.H. reports consultant/advisory roles with Bristol-Myers Squibb, Ono, Merck/Serono and Roche/Genentech, and research funding from MSD. G.G. has no relationships to disclose. J.B. is an employee of Envision Pharma Group. Y.H., K.L., R.W., C.W., and P.A. are employees of Eli Lilly and Company and own stock from Eli Lilly and Company. M. K. has had a consulting/advisory role with Bayer, Bristol-Myers Squibb, Eisai Co., Ltd, MSD and Ono Pharmaceutical, has received honoraria from Bayer, EA Pharma Co., Ltd, Eisai Co., Ltd and MSD, and has received research funding from AbbVie Inc., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, EA Pharma Co., Ltd, Eisai Co., Ltd, Gilead Sciences, Inc., Medico{\textquoteright}s Hirata Inc., Otsuka Pharmaceutical Co., Ltd, Taiho Pharmaceutical and Takeda Pharmaceutical Company Limited. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Cancer Research UK.",
year = "2021",
month = apr,
day = "12",
doi = "10.1038/s41416-021-01260-w",
language = "English",
volume = "124",
pages = "1388--1397",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "8",
}