Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial
Gespeichert in:
| Titel: | Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial |
|---|---|
| Autoren: | Andrew X. Zhu, Bruno Daniele, Guido Gerken, Chia Jui Yen, Izumi Ohno, Giovanni Brandi, Takuji Okusaka, Eric Assenat, Kun-Ming Rau, Marc Pracht, Manabu Morimoto, Josep M. Llovet, Jean-Baptiste Hiriart, Yoon-Koo Kang, Kenta Motomura, Ho Yeong Lim, Richard S. Finn, Philippe Merle, Peter R. Galle, Dong Bok Shin, Paolo Abada, Yanzhi Hsu, Christophe Borg, Masatoshi Kudo |
| Weitere Verfasser: | Harvard Medical School Boston (HMS), Asan Medical Center Seoul, University of Ulsan, National Cheng Kung University (NCKU), David Geffen School of Medicine Los Angeles, University of California Los Angeles (UCLA), University of California (UC)-University of California (UC), University Medical Center Mainz, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Icahn School of Medicine at Mount Sinai New York (MSSM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Alma Mater Studiorum Università di Bologna = University of Bologna (UNIBO), CRLCC Eugène Marquis (CRLCC), UNICANCER, Sungkyunkwan University Suwon (SKKU), Chang Gung Memorial Hospital Taipei (CGMH), Fukuoka University, University of Tokyo Kashiwa Campus, Hôpital de la Croix-Rousse CHU - HCL, Hospices Civils de Lyon (HCL), G Rummo Hospital, Ospedale del Mare, Gachon University Gil Medical Center Incheon, Republic of Korea, Universität Duisburg-Essen = University of Duisburg-Essen Essen, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang Bourgogne-Franche-Comté (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté COMUE (UBFC)-Université Bourgogne Franche-Comté COMUE (UBFC), Hôpital Haut-Lévêque CHU Bordeaux, Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux), Tokyo Medical University, Yokohama University School of Medecine, Eli Lilly and Company Indianapolis, Kindai University |
| Quelle: | The Lancet Oncology. 20:282-296 |
| Verlagsinformationen: | Elsevier BV, 2019. |
| Publikationsjahr: | 2019 |
| Schlagwörter: | MESH: Carcinoma, Male, 0301 basic medicine, Carcinoma, Hepatocellular, Medizin, Liver Neoplasms / blood, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Antibodies, Monoclonal, Humanized, Ramucirumab, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Monoclonal, Humans, Humanized /administration & dosage, Liver Neoplasms / drug therapy, Aged, Neoplasm Staging, Hepatocellular / drug therapy, Antineoplastic Agents / administration & dosage, MESH: Antibodies, Carcinoma, MESH: Alpha-Fetoproteins / analysis, Liver Neoplasms, Middle Aged, Sorafenib, Sorafenib / administration & dosage, 3. Good health, Treatment Outcome, Oncology, Hepatocellular / blood, Drug Therapy, Combination, Female, alpha-Fetoproteins |
| Beschreibung: | Patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations have poor prognosis. We aimed to establish the efficacy of ramucirumab in patients with advanced hepatocellular carcinoma and α-fetoprotein concentrations of 400 ng/mL or higher.REACH-2 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 92 hospitals, clinics, and medical centres in 20 countries. Eligible patients were aged 18 years or older and had histologically or cytologically confirmed hepatocellular carcinoma, or diagnosed cirrhosis and hepatocellular carcinoma, Barcelona Clinic Liver Cancer stage B or C disease, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group (ECOG) performance statuses of 0 or 1, α-fetoprotein concentrations of 400 ng/mL or greater, and had previously received first-line sorafenib. Participants were randomly assigned (2:1) via an interactive web response system with a computer-generated random sequence to 8 mg/kg intravenous ramucirumab every 2 weeks or placebo. All patients received best supportive care. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportion of patients achieving an objective response, time to radiographic progression, safety, time to deterioration in scores on the Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index 8 (FHSI-8), and time to deterioration in ECOG performance status. We also pooled individual patient data from REACH-2 with data from REACH (NCT01140347) for patients with α-fetoprotein concentrations of 400 ng/mL or greater. Efficacy analyses were by intention to treat, whereas safety analyses were done in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02435433.Between July 26, 2015, and Aug 30, 2017, 292 patients were randomly assigned, 197 to the ramucirumab group and 95 to the placebo group. At a median follow-up of 7·6 months (IQR 4·0-12·5), median overall survival (8·5 months [95% CI 7·0-10·6] vs 7·3 months [5·4-9·1]; hazard ratio [HR] 0·710 [95% CI 0·531-0·949]; p=0·0199) and progression-free survival (2·8 months [2·8-4·1] vs 1·6 months [1·5-2·7]; 0·452 [0·339-0·603]; p |
| Publikationsart: | Article |
| Sprache: | English |
| ISSN: | 1470-2045 |
| DOI: | 10.1016/s1470-2045(18)30937-9 |
| Zugangs-URL: | https://pubmed.ncbi.nlm.nih.gov/30665869 https://europepmc.org/article/MED/30665869 https://facultyopinions.com/prime/734883889 https://pubmed.ncbi.nlm.nih.gov/30665869/ https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30937-9/fulltext https://researchoutput.ncku.edu.tw/zh/publications/ramucirumab-after-sorafenib-in-patients-with-advanced-hepatocellu http://www.sciencedirect.com/science/article/pii/S1470204518309379 https://hdl.handle.net/11585/676713 https://doi.org/10.1016/S1470-2045(18)30937-9 http://www.journals.elsevier.com/the-lancet-oncology/ https://www.ncbi.nlm.nih.gov/pubmed/30665869 https://doi.org/10.1016/S1470-2045(18)30937-9 https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&origin=inward&scp=85060887995 |
| Rights: | Elsevier TDM |
| Dokumentencode: | edsair.doi.dedup.....c659e7762c4ea8ec28743092b9b3bf4c |
| Datenbank: | OpenAIRE |
Full Text Finder 
Nájsť tento článok vo Web of Science | Abstract: | Patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations have poor prognosis. We aimed to establish the efficacy of ramucirumab in patients with advanced hepatocellular carcinoma and α-fetoprotein concentrations of 400 ng/mL or higher.REACH-2 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 92 hospitals, clinics, and medical centres in 20 countries. Eligible patients were aged 18 years or older and had histologically or cytologically confirmed hepatocellular carcinoma, or diagnosed cirrhosis and hepatocellular carcinoma, Barcelona Clinic Liver Cancer stage B or C disease, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group (ECOG) performance statuses of 0 or 1, α-fetoprotein concentrations of 400 ng/mL or greater, and had previously received first-line sorafenib. Participants were randomly assigned (2:1) via an interactive web response system with a computer-generated random sequence to 8 mg/kg intravenous ramucirumab every 2 weeks or placebo. All patients received best supportive care. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportion of patients achieving an objective response, time to radiographic progression, safety, time to deterioration in scores on the Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index 8 (FHSI-8), and time to deterioration in ECOG performance status. We also pooled individual patient data from REACH-2 with data from REACH (NCT01140347) for patients with α-fetoprotein concentrations of 400 ng/mL or greater. Efficacy analyses were by intention to treat, whereas safety analyses were done in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02435433.Between July 26, 2015, and Aug 30, 2017, 292 patients were randomly assigned, 197 to the ramucirumab group and 95 to the placebo group. At a median follow-up of 7·6 months (IQR 4·0-12·5), median overall survival (8·5 months [95% CI 7·0-10·6] vs 7·3 months [5·4-9·1]; hazard ratio [HR] 0·710 [95% CI 0·531-0·949]; p=0·0199) and progression-free survival (2·8 months [2·8-4·1] vs 1·6 months [1·5-2·7]; 0·452 [0·339-0·603]; p |
|---|---|
| ISSN: | 14702045 |
| DOI: | 10.1016/s1470-2045(18)30937-9 |