| General information |
| Database: | DB00107 |
| Objective: | VEGF and VEGF receptor2mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor2 antagonist, aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following firstline therapy with sorafenib. |
| Authors: | Zhu AX, et al |
| Title: | Ramucirumab versus placebo as secondline treatment in patients with advanced hepatocellular carcinoma following firstline therapy with sorafenib (REACH): a randomised, doubleblind, multicentre, phase 3 trial. |
| Journal: | Lancet Oncol |
| Year: | 2015 |
| PMID: | 26095784 |
| Trial Design |
| Clinical Trial Id: | NCT01140347 |
| Agent: | ramucirumab
|
| Target: | Vascular endothelial growth factor receptor 2
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a randomised, placebocontrolled, doubleblind, multicentre, phase III trial (REACH) |
| Key Patients Feature: | patients were enrolled from 154 centres in 27 countries, 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 ChildPugh 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. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo+best supportive care |
| Treatment Info: | 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. |
| Primary End Point: | overall survival in the intentiontotreat population |
| Secondary End Point: | NA |
| Patients Number: | 565 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 9.2 vs 7.6(HR 0.87 [95% CI 0.721.05]; p=0.14). |
| Adverse Event(agent arm): | Grade 3 or greater AE 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 (more than and equal to 1%) treatmentemergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression. |
| Conclusions: | Secondline treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals they were noted in eligible patients and the safety profile is manageable. |