| General information |
| Database: | DB00457 |
| Objective: | They assessed whether ramucirumab, a monoclonal antibody VEGFR2 antagonist, in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with placebo plus paclitaxel. |
| Authors: | Wilke H, et al |
| Title: | Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastrooesophageal junction adenocarcinoma (RAINBOW): a doubleblind, randomisedphase 3 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 25240821 |
| Trial Design |
| Clinical Trial Id: | NCT01170663 |
| Agent: | ramucirumab
|
| Target: | Vascular endothelial growth factor receptor 2
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | advanced adenocarcinoma of the stomach or gastroesophageal junction |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Ramucirumab plus paclitaxel |
| Study Type: | a doubleblind, placebocontrolledphase IIItrial |
| Key Patients Feature: | Eligibility criteria included age 18 years and older;having metastatic or nonresectable, locally advancedgastric or gastrooesophageal junction adenocarcinoma;documented objective radiological or clinical diseaseprogression during or within 4 months of the last dose offirstline platinum and fl uoropyrimidine doublet with orwithout anthracycline; an Eastern Cooperative OncologyGroup (ECOG) performance status score of 0 or 1; andmeasureable or nonmeasurable evaluable disease (definedwith Response Evaluation Criteria In Solid Tumors[RECIST], version 1.1).1 |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Ramucirumab plus paclitaxel versus placebo plus paclitaxel |
| Treatment Info: | patients were randomly assigned with a centralised interactive voice or theybresponse system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15, plus paclitaxel 80 mg/m(2) intravenously on days 1, 8, and 15 of a 28day cycle. |
| Primary End Point: | overall survival. |
| Secondary End Point: | Efficacy analysis, and safety analysis. |
| Patients Number: | 665 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | in Ramucirumab plus paclitaxel group (N=330), Complete response <1%, Partial response 27%, Stable disease 52%, Progressive disease 13%; inPlacebo plus paclitaxel group(N=335), Complete response <1%, Partial response 16%, Stable disease 47%, Progressive disease 25%; |
| Disease Control Rate: | ramucirumab plus paclitaxel group vs in the placebo plus paclitaxel group (264 [80%, 95% CI 75-84] vs 213 [64%, 58-69], respectively; p<0.0001). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median progression free survival with ramucirumab plus paclitaxel was signifi cantly longer than with placebo plus paclitaxel (4.4 months [95% CI 4.2-5.3] vs 2.9 months [2.8-3.0]; stratifi ed HR 0.635, [95% CI 0.536-0.752]; p<0.0001) |
| Median OS A vs. C: | Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group (median 9.6 months [95% CI 8.5-10.8] vs7.4 months [95% CI 6.3-8.4], hazard ratio 0.807 [95% CI 0.678-0.962]; p=0.017). |
| Adverse Event(agent arm): | Grade 3 or higher adverse events that occurred in more than 5% of patients in the ramucirumab plus paclitaxel group versus placebo plus paclitaxel included neutropenia (133 [41%] of 327 vs 62 [19%] of 329), leucopenia (57 [17%] vs 22 [7%]), hypertension (46 [14%] vs eight [2%]), fatigue (39 [12%] vs 18 [5%]), anaemia (30 [9%] vs 34 [10%]), and abdominal pain (20 [6%] vs 11 [3%]). The incidence of grade 3 or higher febrile neutropenia was low in both groups (ten [3%] vs eight [2%]). |
| Conclusions: | The combination of ramucirumab with paclitaxel significantly increases overall survival compared with placebo plus paclitaxel, and could be regarded as a new standard secondline treatment for patients with advanced gastric cancer. |