Ramucirumab significantly improved both progression-free and overall survival, when added to paclitaxel in second-line therapy for metastatic gastric cancer, according to the results of a study presented at the 2014 Gastrointestinal Cancers Symposium.
Gastric cancer refers to cancer of the stomach. Though gastric cancer has a relatively low incidence in the United States, it is the second leading cause of cancer death worldwide. The incidence of gastric cancer is quite high in Asian countries such as Korea, China, Taiwan, and Japan. Treatment of gastric cancer typically involves surgical removal of the cancer followed by the use of chemotherapy with or without radiation therapy.
Ramucirumab is a type of targeted agent known as a monoclonal antibody. It blocks VEGFR-2 and starves tumors of nutrients needed to grow.
The RAINBOW trial was a randomized, double-blind, placebo-controlled, phase III study that included 665 patients with metastatic gastroesophageal junction or gastric adenocarcinoma who had disease progression while on or within 4 months after a standard first-line chemotherapy regimen. Patients in the study were randomly assigned to receive ramucirumab plus paclitaxel or paclitaxel alone until disease progression or intolerable toxicity. The primary endpoint was overall survival.
The results showed an advantage with the addition of ramucirumab. Median overall survival was 9.6 months for patients who received ramucirumab/paclitaxel compared with 7.4 months for those who received paclitaxel alone. This reflected a 19 percent reduction in the risk of death with ramucirumab/paclitaxel. Median progression-free survival was 4.4 months with ramucirumab/paclitaxel, compared to 2.9 months with paclitaxel alone. Median time to progression was 5.5 months and 3.0 months, respectively.
The objective response rate with ramucirumab/paclitaxel was 28 percent compared to 16 percent with paclitaxel alone and the disease control rate was 80 percent and 64 percent, respectively.
Grade 3 or higher adverse events were more common in the ramucirumab/paclitaxel group (82% vs 63%) and these included neutropenia, leukopenia, hypertension, and fatigue. Grade 3 and 4 neutropenia occurred more frequently in the ramucirumab/paclitaxel, but the incidence of febrile neutropenia was comparable between the two groups.
The researchers concluded that ramucirumab significantly improved both progression-free and overall survival, when added to paclitaxel in second-line therapy for metastatic gastric cancer. They note that “A statistically significant and clinically meaningful overall survival benefit of more than 2 months was observed for ramucirumab plus paclitaxel versus paclitaxel alone.”
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 paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-JVBE). Presented at the 2014 Gastrointestinal Cancers Symposium. Journal of Clinical Oncology. 2014; 32 (supplement 3; abstract LBA7).