J 2020

Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2

KUDO, M., P. R. GALLE, J. M. LLOVET, R. S. FINN, A. VOGEL et. al.

Basic information

Original name

Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2

Authors

KUDO, M. (392 Japan, guarantor), P. R. GALLE (276 Germany), J. M. LLOVET (724 Spain), R. S. FINN (840 United States of America), A. VOGEL (276 Germany), K. MOTOMURA (392 Japan), E. ASSENAT (250 France), P. MERLE (380 Italy), G. BRANDI (380 Italy), B. DANIELE (380 Italy), T. OKUSAKA (392 Japan), Jiří TOMÁŠEK (203 Czech Republic, belonging to the institution), C. BORG (250 France), V. DADDUZIO (380 Italy), M. MORIMOTO (392 Japan), M. PRACHT (250 France), M. H. JEN (826 United Kingdom of Great Britain and Northern Ireland), N. D. UBREVA (392 Japan), R. C. WIDAU (840 United States of America), K. SHINOZAKI (392 Japan), R. YOSHIKAWA (392 Japan) and A. X. ZHU (840 United States of America)

Edition

Liver International, Hoboken, John Viley & Sons, 2020, 1478-3223

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30219 Gastroenterology and hepatology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.828

RIV identification code

RIV/00216224:14110/20:00116137

Organization unit

Faculty of Medicine

DOI

UT WoS

000530611100001

Keywords in English

alpha-fetoprotein (AFP); elderly; hepatocellular carcinoma; ramucirumab; sorafenib intolerance; VEGFR2

Tags

Tags

International impact, Reviewed
Změněno: 5/8/2020 14:30, Mgr. Tereza Miškechová

Abstract

V originále

Background & Aims Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha-fetoprotein (AFP) >= 400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP >= 400 ng/mL by three prespecified age subgroups (<65, >= 65 to <75 and >= 75 years). Methods Individual patient data were pooled from REACH (baseline AFP >= 400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP) and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). Results A total of 542 patients (<65 years: n = 302; >= 65 to <75 years: n = 160; >= 75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), >= 65 to <75 years (0.602; 0.419-0.866) and >= 75 years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity >= 97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. Conclusions In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with elevated AFP, irrespective of age, including >= 75 years.