Galle, Peter R; Kudo, Masatoshi; Llovet, Josep M; Finn, Richard S; Karwal, Mark; Pezet, Denis; Kim, Tae-You; Yang, Tsai-Sheng; Lonardi, Sara; Tomasek, Jiri; Phelip, Jean-Marc; Touchefeu, Yann; Koh, Su-Jin; Stirnimann, Guido; Liang, Kun; Ogburn, Kenyon D; Wang, Chunxiao; Abada, Paolo; Widau, Ryan C and Zhu, Andrew X (2021). Ramucirumab in patients with previously treated advanced hepatocellular carcinoma: Impact of liver disease aetiology. Liver international, 41(11), pp. 2759-2767. Wiley 10.1111/liv.14994
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology |
UniBE Contributor: |
Stirnimann, Guido |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1478-3231 |
Publisher: |
Wiley |
Language: |
English |
Submitter: |
Rahel Fuhrer |
Date Deposited: |
29 Aug 2021 22:49 |
Last Modified: |
05 Dec 2022 15:52 |
Publisher DOI: |
10.1111/liv.14994 |
PubMed ID: |
34173317 |
Uncontrolled Keywords: |
hepatitis B hepatitis C hepatocellular carcinoma ramucirumab |
BORIS DOI: |
10.48350/157994 |
URI: |
https://boris.unibe.ch/id/eprint/157994 |
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