@article{cff8fbb9d6c64a6e971cf0b5051f4450,
title = "Ramucirumab in patients with previously treated advanced hepatocellular carcinoma: Impact of liver disease aetiology",
abstract = "Background & Aims: Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease with diverse underlying aetiologies. REACH/REACH-2 were global phase III studies investigating ramucirumab in advanced HCC (aHCC) following sorafenib treatment. We performed an exploratory analysis of outcomes by liver disease aetiology and baseline serum viral load. Methods: Meta-analysis was conducted in patients with aHCC and alpha-fetoprotein (AFP) ≥400 ng/mL (N = 542) from REACH/REACH-2 trials. Individual patient-level data were pooled with results reported by aetiology subgroup (hepatitis B [HBV] or C [HCV] and Other). Pre-treatment serum HBV DNA and HCV RNA were quantified using Roche COBAS AmpliPrep/COBAS TaqMan. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox proportional hazard model (stratified by study). Results: Baseline characteristics were generally balanced between arms in each subgroup (HBV: N = 225, HCV: N = 127, Other: N = 190). No significant difference in treatment effect by aetiology subgroup was detected (OS interaction P-value =.23). Median OS (ramucirumab vs placebo) in months was 7.7 versus 4.5 (HR 0.74, 95% CI 0.55–0.99) for HBV, 8.2 versus 5.5 (HR 0.82, 95% CI 0.55–1.23) for HCV and 8.5 versus 5.4 (HR 0.56, 95% CI 0.40–0.79) for Other. Ramucirumab showed similar overall safety profiles across subgroups. Worst outcomes were noted in patients with a detectable HBV load. Use of HBV antiviral therapy, irrespective of viral load, was beneficial for survival, liver function and liver-specific adverse events. Conclusions: Ramucirumab improved survival across aetiology subgroups with a tolerable safety profile, supporting its use in patients with aHCC and elevated AFP.",
keywords = "hepatitis B, hepatitis C, hepatocellular carcinoma, ramucirumab",
author = "Galle, {Peter R.} and Masatoshi Kudo and Llovet, {Josep M.} and Finn, {Richard S.} and Mark Karwal and Denis Pezet and Kim, {Tae You} and Yang, {Tsai Sheng} and Sara Lonardi and Jiri Tomasek and Phelip, {Jean Marc} and Yann Touchefeu and Koh, {Su Jin} and Guido Stirnimann and Kun Liang and Ogburn, {Kenyon D.} and Chunxiao Wang and Paolo Abada and Widau, {Ryan C.} and Zhu, {Andrew X.}",
note = "Funding Information: reports grants from Bayer and Eli Lilly and Company, personal fees from BMS, AstraZeneca, Sirtex, MSD, Eisai, Ipsen, Bayer, and Roche, and other from Eli Lilly and Company. . reports grant and personal fees from Eisai and EA Pharma; grants from Gilead Sciences, Taiho, Sumitomo Dainippon Pharma, Takeda, Otsuka, and Abbvie; and personal fees from Roche, Ono, Eli Lilly and Company, BMS, and Bayer. . reports grants and personal fees from Bayer Pharmaceuticals, Eisai, Boehringer Ingelheim, & Ipsen, grants from Bristol Myers Squibb, and personal fees from Eli Lilly and Company, Celsion, Merck, Genentech, Roche, Glycotest, Nucleix, Sirtex, Mina Alpha, Astrazeneca, Axis, and Medscape. . reports personal fees from AstraZeneca and Cstone; grants and personal fees from Bayer, Eisai, Bristol‐Myers Squibb, Roche/ Genentech, Merck, Pfizer and Eli Lilly and Company. . reports grants from Eli Lilly and Company, and other from Eisai. . has nothing to disclose. . has nothing to disclose. . has nothing to disclose. . reports grants and other from Amgen, Merck Serono, Eli Lilly and Company, Astra Zeneca, Bristol‐Myer Squibb, Roche, grants from Bayer, and other from Incyte, Daiichi Sankyo, Servier, Glaxo‐Smith Kline and Pierre‐Fabre. . has nothing to disclose. . reports grants, personal fees and non‐financial support from Eli Lilly and Company and personal fees and non‐financial support from Servier. . has nothing to disclose. . has nothing to disclose. . reports personal fees from Eli Lilly and Company. . is a former employee and shareholder of Eli Lilly and Company and has nothing further to disclose. . is a former employee and shareholder of Eli Lilly and Company and is currently employed by AstraZeneca. . is an employee and shareholder of Eli Lilly and Company. . is an employee and shareholder of Eli Lilly and Company. . is an employee and shareholder of Eli Lilly and Company. . reports personal fees from Roche, Eli Lilly and Company, Eisai, Bayer, Merck, Exelixis & Sanofi. P. Galle M Kudo J Llovet R Finn M Karwal D Pezet T. Y Kim T. S Yang S Lonardi J Tomasek J. M Phelip Y Touchefeu S. J Koh G Stirnimann K Liang K Ogburn C Wang P Abada R Widau A Zhu Funding Information: This study was funded by Eli Lilly and Company (grant numbers not applicable) The authors gratefully acknowledge Laura Ramsey, David McIlwain, and Louise McGrath, employees of Eli Lilly and Company, and Andrea Humphries of Syneos Health, for providing editorial and process support. Publisher Copyright: {\textcopyright} 2021 The Authors. Liver International published by John Wiley & Sons Ltd.",
year = "2021",
month = nov,
doi = "10.1111/liv.14994",
language = "English",
volume = "41",
pages = "2759--2767",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "11",
}