A global phase III trial of Cyramza (ramucirumab) in combination with paclitaxel in patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma met its primary endpoint of median overall survival.
In the trial, known as RAINBOW, the addition of ramucirumab to paclitaxel also met secondary endpoints of progression-free survival and objective response rate. The global, double-blinded study enrolled a total of 665 patients refractory to or progressive after initial platinum- and fluoropyrimidine-containing chemotherapy.
Patients randomized to receive ramucirumab plus paclitaxel had a median survival benefit of 9.6 months, compared to 7.4 months for patients who received paclitaxel and placebo (stratified HR 0.807 [95% CI, 0.678-0.962; p=0.0169]).
Treatment with ramucirumab plus paclitaxel significantly reduced the risk of disease progression or death by 37 percent, with a 52 percent increase in median progression-free survival compared with placebo plus paclitaxel (4.4 vs. 2.9 months; stratified HR 0.635 [95% CI, 0.536-0.752; p < 0.0001]).
There was a statistically significant increase in objective response rate, from 16 to 28 percent, with the addition of ramucirumab (p=0.0001).
RAINBOW is the largest trial in second-line gastric cancer to date and the first phase III study to demonstrate a survival benefit with a biologic used in combination with chemotherapy in this setting, according to the drug’s sponsor, Eli Lilly and Company. Data were published in The Lancet Oncology, after being first presented at the Gastrointestinal Cancers Symposium in January.
Grade 3 or higher adverse events occurred at a higher rate and for more than 10 percent of patients on the ramucirumab-plus-paclitaxel arm: neutropenia; leukopenia; hypertension; and fatigue. Febrile neutropenia incidence was low in both trial arms, at 3 and 2 percent, respectively.
Cyramza is approved for use as a single agent in the U.S. for patients with advanced gastric or gastroesophageal junction adenocarcinoma who have progressed after prior fluoropyrimidine- or platinum-containing chemotherapy. Cyramza is a VEGF Receptor 2 antagonist that specifically binds and blocks activation of VEGF Receptor 2 and blocks binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D.
There are several studies underway or planned to investigate Cyramza as a single agent and in combination with other anti-cancer therapies for the treatment of multiple tumor types.
Data from the RAINBOW trial are the basis for regulatory submissions in the U.S. and the European Union, according to Eli Lilly, and the company is planning a submission to Japanese regulatory authorities in the second half of 2014.
