Phase 3 data from a global clinical trial indicated an improvement in overall survival (OS) when the investigational angiogenesis inhibitor ramucirumab was 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 known as RAINBOW (Study of Paclitaxel With or Without Ramucirumab in Metastatic Gastric Adenocarcinoma), said lead investigator Hansjochen Wilke, MD, 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 [GEJ] cancer,” said Wilke, director of the Department of Oncology/Hematology and Center of Palliative Care, Kliniken Essen-Mitte, Germany.
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, noted Smitha Krishnamurthi, MD, 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 Krishnamurthi, associate professor of medicine, Division of Hematology and Oncology, at Case Western Reserve University School of Medicine, Cleveland, Ohio.
RAINBOW involved 665 patients with metastatic GEJ or gastric adenocarcinoma who exhibited disease progression within 4 months after standard first-line chemotherapy with platinum- and fluoro-
pyrimidine-based combinations. Patients were randomized to either a combination of ramucirumab and paclitaxel or paclitaxel alone. Treatment was administered until disease progression, unacceptable toxicity, or death.
Adding ramucirumab to second-line paclitaxel significantly improved response rates, OS, and progression-free survival (PFS). The objective response rates were 28% in patients randomized to ramucirumab plus paclitaxel compared with 16% in patients randomized to paclitaxel alone (P = .0001).
The median OS was 9.6 months in the ramucirumab plus paclitaxel arm and 7.4 months in the paclitaxel-only arm, corresponding to a 20% reduction in the hazard ratio with ramucirumab (P = .0169). Six-month survival was 72% versus 57%, and 12-month survival was 40% versus 30% in the ramucirumab plus paclitaxel and paclitaxel-only arms, respectively.
Median PFS was 4.4 months for the combination of ramucirumab and pac-litaxel compared with 2.9 months for paclitaxel alone, corresponding to a 36% reduction in risk (P <.0001).
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 frequently reported in the ramucirumab plus paclitaxel group, the incidence of febrile neutropenia was comparable to treatment with paclitaxel alone. All of these side effects were manageable, and very few patients discontinued treatment due to toxicities.
The most common grade 3 adverse events with ramucirumab were neutropenia (40.7% vs 18.8% in the paclitaxel- only group), leukopenia (17.4% vs 6.7%), and fatigue (11.9% vs 5.5%); febrile neutropenia occurred with similar frequency in both groups (3.1% vs 2.4%).
Other grade 3 adverse events that occurred more often with ramucirumab compared with paclitaxel alone were hypertension (14.7% vs 2.7%), bleeding/hemorrhage (4.3% vs 2.4%), gastrointestinal bleeding (3.7% vs 1.5%), proteinuria (1.2% vs 0%), and gastrointestinal perforation (1.2% vs 0%).
Wilke H, Van Cutsem E, Oh SC, et al. RAINBOW: a global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus pac-litaxel in the treatment of metastatic gastroesophage-
al junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-JVBE). J Clin Oncol. 2014;32(suppl 3):Abstract LBA7. Presented at: 2014 Gastrointestinal Cancers Symposium; January 16-18, 2014; San Francisco, CA.