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Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial

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Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. / Zhu, Andrew X; Park, Joon Oh; Ryoo, Baek-Yeol; Yen, Chia-Jui; Poon, Ronnie; Pastorelli, Davide; Blanc, Jean-Frederic; Chung, Hyun Cheol; Baron, Ari D; Pfiffer, Tulio Eduardo Flesch; Okusaka, Takuji; Kubackova, Katerina; Trojan, Jorg; Sastre, Javier; Chau, Ian; Chang, Shao-Chun; Abada, Paolo B; Yang, Ling; Schwartz, Jonathan D; Kudo, Masatoshi; REACH Trial Investigators.

in: LANCET ONCOL, Jahrgang 16, Nr. 7, 07.2015, S. 859-70.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Zhu, AX, Park, JO, Ryoo, B-Y, Yen, C-J, Poon, R, Pastorelli, D, Blanc, J-F, Chung, HC, Baron, AD, Pfiffer, TEF, Okusaka, T, Kubackova, K, Trojan, J, Sastre, J, Chau, I, Chang, S-C, Abada, PB, Yang, L, Schwartz, JD, Kudo, M & REACH Trial Investigators 2015, 'Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial', LANCET ONCOL, Jg. 16, Nr. 7, S. 859-70. https://doi.org/10.1016/S1470-2045(15)00050-9

APA

Zhu, A. X., Park, J. O., Ryoo, B-Y., Yen, C-J., Poon, R., Pastorelli, D., Blanc, J-F., Chung, H. C., Baron, A. D., Pfiffer, T. E. F., Okusaka, T., Kubackova, K., Trojan, J., Sastre, J., Chau, I., Chang, S-C., Abada, P. B., Yang, L., Schwartz, J. D., ... REACH Trial Investigators (2015). Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. LANCET ONCOL, 16(7), 859-70. https://doi.org/10.1016/S1470-2045(15)00050-9

Vancouver

Zhu AX, Park JO, Ryoo B-Y, Yen C-J, Poon R, Pastorelli D et al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. LANCET ONCOL. 2015 Jul;16(7):859-70. https://doi.org/10.1016/S1470-2045(15)00050-9

Bibtex

@article{ad8a4ad6c15c4b46acc27ab04f641a34,
title = "Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial",
abstract = "BACKGROUND: VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib.METHODS: In this randomised, placebo-controlled, double-blind, multicentre, phase 3 trial (REACH), patients were enrolled from 154 centres in 27 countries. Eligible patients were aged 18 years or older, had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy, had Child-Pugh A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, had previously received sorafenib (stopped because of progression or intolerance), and had adequate haematological and biochemical parameters. Patients were randomly assigned (1:1) to receive intravenous ramucirumab (8 mg/kg) or placebo every 2 weeks, plus best supportive care, until disease progression, unacceptable toxicity, or death. Randomisation was stratified by geographic region and cause of liver disease with a stratified permuted block method. Patients, medical staff, investigators, and the funder were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01140347.FINDINGS: Between Nov 4, 2010, and April 18, 2013, 565 patients were enrolled, of whom 283 were assigned to ramucirumab and 282 were assigned to placebo. Median overall survival for the ramucirumab group was 9·2 months (95% CI 8·0-10·6) versus 7·6 months (6·0-9·3) for the placebo group (HR 0·87 [95% CI 0·72-1·05]; p=0·14). Grade 3 or greater adverse events occurring in 5% or more of patients in either treatment group were ascites (13 [5%] of 277 patients treated with ramucirumab vs 11 [4%] of 276 patients treated with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (≥1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression.INTERPRETATION: Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable.FUNDING: Eli Lilly and Co.",
keywords = "Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Carcinoma, Hepatocellular, Confidence Intervals, Disease-Free Survival, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Liver Neoplasms, Male, Middle Aged, Niacinamide, Patient Selection, Phenylurea Compounds, Proportional Hazards Models, Remission Induction, Survival Analysis, Time Factors, Treatment Outcome, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",
author = "Zhu, {Andrew X} and Park, {Joon Oh} and Baek-Yeol Ryoo and Chia-Jui Yen and Ronnie Poon and Davide Pastorelli and Jean-Frederic Blanc and Chung, {Hyun Cheol} and Baron, {Ari D} and Pfiffer, {Tulio Eduardo Flesch} and Takuji Okusaka and Katerina Kubackova and Jorg Trojan and Javier Sastre and Ian Chau and Shao-Chun Chang and Abada, {Paolo B} and Ling Yang and Schwartz, {Jonathan D} and Masatoshi Kudo and {REACH Trial Investigators}",
note = "Copyright {\textcopyright} 2015 Elsevier Ltd. All rights reserved.",
year = "2015",
month = jul,
doi = "10.1016/S1470-2045(15)00050-9",
language = "English",
volume = "16",
pages = "859--70",
journal = "LANCET ONCOL",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
number = "7",

}

RIS

TY - JOUR

T1 - Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial

AU - Zhu, Andrew X

AU - Park, Joon Oh

AU - Ryoo, Baek-Yeol

AU - Yen, Chia-Jui

AU - Poon, Ronnie

AU - Pastorelli, Davide

AU - Blanc, Jean-Frederic

AU - Chung, Hyun Cheol

AU - Baron, Ari D

AU - Pfiffer, Tulio Eduardo Flesch

AU - Okusaka, Takuji

AU - Kubackova, Katerina

AU - Trojan, Jorg

AU - Sastre, Javier

AU - Chau, Ian

AU - Chang, Shao-Chun

AU - Abada, Paolo B

AU - Yang, Ling

AU - Schwartz, Jonathan D

AU - Kudo, Masatoshi

AU - REACH Trial Investigators

N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.

PY - 2015/7

Y1 - 2015/7

N2 - BACKGROUND: VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib.METHODS: In this randomised, placebo-controlled, double-blind, multicentre, phase 3 trial (REACH), patients were enrolled from 154 centres in 27 countries. Eligible patients were aged 18 years or older, had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy, had Child-Pugh A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, had previously received sorafenib (stopped because of progression or intolerance), and had adequate haematological and biochemical parameters. Patients were randomly assigned (1:1) to receive intravenous ramucirumab (8 mg/kg) or placebo every 2 weeks, plus best supportive care, until disease progression, unacceptable toxicity, or death. Randomisation was stratified by geographic region and cause of liver disease with a stratified permuted block method. Patients, medical staff, investigators, and the funder were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01140347.FINDINGS: Between Nov 4, 2010, and April 18, 2013, 565 patients were enrolled, of whom 283 were assigned to ramucirumab and 282 were assigned to placebo. Median overall survival for the ramucirumab group was 9·2 months (95% CI 8·0-10·6) versus 7·6 months (6·0-9·3) for the placebo group (HR 0·87 [95% CI 0·72-1·05]; p=0·14). Grade 3 or greater adverse events occurring in 5% or more of patients in either treatment group were ascites (13 [5%] of 277 patients treated with ramucirumab vs 11 [4%] of 276 patients treated with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (≥1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression.INTERPRETATION: Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable.FUNDING: Eli Lilly and Co.

AB - BACKGROUND: VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib.METHODS: In this randomised, placebo-controlled, double-blind, multicentre, phase 3 trial (REACH), patients were enrolled from 154 centres in 27 countries. Eligible patients were aged 18 years or older, had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy, had Child-Pugh A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, had previously received sorafenib (stopped because of progression or intolerance), and had adequate haematological and biochemical parameters. Patients were randomly assigned (1:1) to receive intravenous ramucirumab (8 mg/kg) or placebo every 2 weeks, plus best supportive care, until disease progression, unacceptable toxicity, or death. Randomisation was stratified by geographic region and cause of liver disease with a stratified permuted block method. Patients, medical staff, investigators, and the funder were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01140347.FINDINGS: Between Nov 4, 2010, and April 18, 2013, 565 patients were enrolled, of whom 283 were assigned to ramucirumab and 282 were assigned to placebo. Median overall survival for the ramucirumab group was 9·2 months (95% CI 8·0-10·6) versus 7·6 months (6·0-9·3) for the placebo group (HR 0·87 [95% CI 0·72-1·05]; p=0·14). Grade 3 or greater adverse events occurring in 5% or more of patients in either treatment group were ascites (13 [5%] of 277 patients treated with ramucirumab vs 11 [4%] of 276 patients treated with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (≥1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression.INTERPRETATION: Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable.FUNDING: Eli Lilly and Co.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Monoclonal

KW - Carcinoma, Hepatocellular

KW - Confidence Intervals

KW - Disease-Free Survival

KW - Dose-Response Relationship, Drug

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Kaplan-Meier Estimate

KW - Liver Neoplasms

KW - Male

KW - Middle Aged

KW - Niacinamide

KW - Patient Selection

KW - Phenylurea Compounds

KW - Proportional Hazards Models

KW - Remission Induction

KW - Survival Analysis

KW - Time Factors

KW - Treatment Outcome

KW - Clinical Trial, Phase III

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/S1470-2045(15)00050-9

DO - 10.1016/S1470-2045(15)00050-9

M3 - SCORING: Journal article

C2 - 26095784

VL - 16

SP - 859

EP - 870

JO - LANCET ONCOL

JF - LANCET ONCOL

SN - 1470-2045

IS - 7

ER -