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 - 30/06/15
, Joon Oh Park, MD b, Baek-Yeol Ryoo, MD c, Chia-Jui Yen, MD d, Ronnie Poon, MD e, Davide Pastorelli, MD f, Jean-Frederic Blanc, MD g, Hyun Cheol Chung, MD h, Ari D Baron, MD i, Tulio Eduardo Flesch Pfiffer, MD j, Takuji Okusaka, MD k, Katerina Kubackova, MD l, Jorg Trojan, MD m, Javier Sastre, PhD n, Ian Chau, MD o, Shao-Chun Chang, MD p, Paolo B Abada, MD p, Ling Yang, MS q, Jonathan D Schwartz, MD r, Masatoshi Kudo, MD sfor the
REACH Trial Investigators†
Summary |
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.
Le texte complet de cet article est disponible en PDF.Plan
Vol 16 - N° 7
P. 859-870 - juillet 2015 Retour au numéro
Article précédent
- Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials
- Jürg Bernhard, Weixiu Luo, Karin Ribi, Marco Colleoni, Harold J Burstein, Carlo Tondini, Graziella Pinotti, Simon Spazzapan, Thomas Ruhstaller, Fabio Puglisi, Lorenzo Pavesi, Vani Parmar, Meredith M Regan, Olivia Pagani, Gini F Fleming, Prudence A Francis, Karen N Price, Alan S Coates, Richard D Gelber, Aron Goldhirsch, Barbara A Walley
- Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology
- Khê Hoang-Xuan, Eric Bessell, Jacoline Bromberg, Andreas F Hottinger, Matthias Preusser, Roberta Rudà, Uwe Schlegel, Tali Siegal, Carole Soussain, Ufuk Abacioglu, Nathalie Cassoux, Martina Deckert, Clemens M F Dirven, Andrés J M Ferreri, Francesc Graus, Roger Henriksson, Ulrich Herrlinger, Martin Taphoorn, Riccardo Soffietti, Michael Weller, European Association for Neuro-Oncology Task Force on Primary CNS Lymphoma
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?