Subsequently, the REGARD study evaluated the anti-VEGFR-2 monoclonal antibody ramucirumab in 355 patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma following progression on first-line therapy. Patients were randomized to ramucirumab versus placebo. Ramucirumab significantly improved OS (5.2 months versus 3.8 months for placebo) and progression-free survival (PFS; median of 2.1 months versus 1.3 months for placebo).
Twelve-week PFS was 40% versus 16% for placebo. Toxicities were comparable between the ramucirumab and placebo groups; adverse events of any grade were reported by 57% of the ramucirumab group and 58% of the placebo group.
As might be expected, more patients treated with the antiangiogenesis drug had hypertension (8% versus 3% in the placebo group for any grade hypertension). No important toxicity signals emerged in this trial.
Ramucirumab achieved similar OS to docetaxel or irinotecan versus best supportive care in other phase III trials, according to Fuchs. “We see a similar benefit with ramucirumab as with other agents, but a better toxicity profile. It is important to look at toxicity when the drug is added to chemotherapy,” Fuchs said.
Based on results of the REGARD study, the FDA granted priority review to ramucirumab.
A combination strategy with ramucirumab is also being explored. The RAINBOW study randomized 663 patients with metastatic gastric cancer who failed on first-line therapy to paclitaxel plus ramucirumab or paclitaxel plus placebo (NCT01170663). A preliminary news release reported significant improvement in PFS and OS in those treated with ramucirumab.
“We will need to see more details on the results,” Fuchs said.
Fuchs, C. Novel agents in gastric cancer. Presented at: 2013 Chemotherapy Foundation Symposium; November 6-8, 2013; New York City.