Ramucirumab Combination Improves Overall Survival After First Progression in Patients With Metastatic Gastric Cancer
In the global phase III RAINBOW trial of patients with metastatic gastric cancer, the investigational monoclonal antibody ramucirumab significantly improved both progression-free and overall survival when given as second-line therapy, investigators reported at a press briefing in advance of the 2014 Gastrointestinal Cancers Symposium (Abstract LBA7).
Median overall survival for patients receiving ramucirumab plus paclitaxel was 9.6 months, compared to 7.4 months for those receiving only paclitaxel.
“The primary endpoint of improved overall survival was met,” Hansjochen Wilke, MD, of the Kliniken Essen-Mitte in Essen, Germany. “The 2.3-month difference in overall survival is an astonishingly good result in this poor-prognosis population. The difference is not only statistically significant but clinically meaningful.”
Ramucirumab is a human IgG1 monoclonal antibody that blocks the vascular endothelial growth factor receptor 2 (VEGFR-2), and therefore thwarts angiogenesis.
Dr. Wilke noted that patients with disease progression after first-line treatment have a poor prognosis, with a median survival of about 3 months. Only about one-third of patients in the United States receive second-line therapy. RAINBOW is the largest clinical trial of second-line therapy in this patient population to date.
RAINBOW Details
The study included 665 patients with metastatic gastroesophageal junction or gastric adenocarcinoma who had disease progression while on or within 4 months of standard first-line platinum- and fluoropyrimidine-based combination chemotherapy. Patients were randomly assigned to receive paclitaxel alone (80 mg/m2 on days 1, 8, 15) or with ramucirumab (8 mg/kg IV every 2 weeks) in 4-week cycles indefinitely. The primary endpoint was overall survival.
Median overall survival was 9.6 months for the combination and 7.4 months for paclitaxel alone, representing a 19% reduction in risk (P = .0169) with ramucirumab. Median progression-free survival was 4.4 months and 2.9 months, respectively, a 27% reduction in risk (P < .0001). The objective response rate associated with the combination was 28% vs 16% with paclitaxel alone (P = .0001), Dr. Wilke reported.
“Progression-free survival was almost doubled at 6 months with ramucirumab plus paclitaxel vs paclitaxel alone,” he noted.
At 6 months, the progression-free survival rate was 36% vs 17%, and at 9 months was 22% vs 10%, respectively. In addition, the disease control rate was much better with ramucirumab, 80% vs 64%, respectively (P < .0001).
Manageable Side Effects
Adverse events of grade ≥ 3 were somewhat greater with ramucirumab/paclitaxel, including neutropenia (40.7% vs 18.8%), leukopenia (17.4% vs 6.7%), hypertension (14.1% vs 2.4%), anemia (9.2% vs 10.3%), fatigue (7.0% vs 4.0%), abdominal pain (5.5% vs 3.3%), and asthenia (5.5% vs 3.3%).
“Neutropenia was more frequently reported in the ramucirumab/paclitaxel arm, but the incidence of febrile neutropenia was comparable [3.1% vs 2.4%],” Dr. Wilke said. “Febrile neutropenia was not a problem. The combination was safe and manageable.”
He concluded, “RAINBOW clearly demonstrates that ramuricumab is an effective new drug for metastatic or locally advanced gastric cancer patients [for whom] first-line platinum- and fluoropyrimidine-based combination chemotherapy [has failed]. It also shows that an effective second-line therapy improves survival. I believe that more patients will now routinely be treated in the second-line setting.”
Smitha Krishnamurthi, MD, Associate Professor of Medicine at University Hospitals of Case Medical Center and Case Western Reserve University, who moderated the press briefing, noted that RAINBOW is “a very large study for second-line metastatic gastric cancer, and it is the only study to show a 2-month improvement in survival.”
For full disclosures of the study authors, view the study abstract at www.gicasym.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
