Ramucirumab Improves Survival as Second-Line Therapy in Patients with Advanced Gastric Cancer
San Francisco, CA—Phase 3 data from a global clinical trial have demonstrated an improvement in overall survival (OS) when the investigational angiogenesis inhibitor ramucirumab is added to chemotherapy as second-line therapy in patients with advanced gastric cancer.
The improvement in survival was more than 2 months with ramucirumab when used after progression with first-line therapy in the Study of Paclitaxel with or without Ramucirumab in Metastatic Gastric Adenocarcinoma (RAINBOW), said lead investigator Hansjochen Wilke, MD, PhD, Director, Department of Oncology/Hematology and Center of Palliative Care, Kliniken Essen-Mitte, Germany, at the 2014 Gastrointestinal Cancers Symposium.
“This trial, and the recently published REGARD trial, demonstrate that ramucirumab is an effective new drug for the treatment of patients with metastatic or locally advanced unresectable gastric cancer and gastroesophageal junction cancer,” said Dr Wilke.
Ramucirumab, a human IgG1 monoclonal antibody that blocks the vascular endothelial growth factor receptor 2, represents the only second-line agent to extend life by as much as 2 months for patients with advanced gastric cancer, commented Smitha S. Krishnamurthi, MD, Associate Professor of Medicine, Division of Hematology and Oncology, Case Western Reserve University School of Medicine, Cleveland, OH, who was not involved in the study.
“We’re excited to have what appears to be an active drug in the second-line setting that can be used instead of best supportive care or in addition to second-line chemotherapy for patients who can tolerate chemotherapy,” said Dr Krishnamurthi.
RAINBOW involved 665 patients with metastatic gastroesophageal junction or gastric adenocarcinoma who exhibited disease progression within 4 months after standard first-line chemotherapy with platinum- and fluoropyrimidine-based combinations. The patients were randomized to a regimen of ramucirumab and paclitaxel or to paclitaxel alone.
Treatment was administered in 4-week cycles until disease progression, unacceptable toxicity, or death.
Adding ramucirumab to second-line paclitaxel significantly improved response rates, OS, and progression-free survival (PFS). The overall response rates were 28% in patients randomized to ramucirumab plus paclitaxel compared with 16% of patients randomized to paclitaxel alone (P = .001).
The median OS improved from 7.4 months with paclitaxel only to 9.6 months with the ramucirumab plus paclitaxel regimen, corresponding to a 20% reduction in the hazard ratio with ramucirumab (P = .0169).
The 6-month survival rate was 72% versus 57%, and the 12-month survival rate was 40% versus 30% in the ramucirumab/paclitaxel arm versus the paclitaxel only arm, respectively.
The median PFS was 4.4 months with the ramucirumab/paclitaxel regimen compared with 2.9 months for paclitaxel alone, corresponding to a 36% (P <.001) reduction in risk.
Patients who received ramucirumab plus paclitaxel also reported a reduction in pain and other improvements in their quality of life.
The most common side effects of treatment with ramucirumab and paclitaxel include neutropenia, leukopenia, hypertension, anemia, fatigue, abdominal pain, and asthenia. Although neutropenia was more often reported in the ramucirumab plus paclitaxel group, the incidence of febrile neutropenia was comparable to treatment with paclitaxel alone. All the side effects were manageable, and very few patients discontinued treatment because of them.
The most common grade ?3 adverse events with ramucirumab were neutropenia (40.7% vs 18.8% in the placebo group), leukopenia (17.4% vs 6.7%, respectively), and fatigue (11.9% vs 5.5%, respectively); febrile neutropenia occurred with similar frequency in both groups (3.1% vs 2.4%, respectively).
Other grade ?3 adverse events that occurred more often with ramucirumab compared with placebo were hypertension (14.7% vs 2.7%, respectively), bleeding/hemorrhage (4.3% vs 2.4%, respectively), gastrointestinal bleeding (3.7% vs 1.5%, respectively), proteinuria (1.2% vs 0%, respectively), and gastrointestinal perforation (1.2% vs 0%, respectively).