Eli Lilly and Company announced that results of the global phase III trial of ramucirumab (Cyramza) in combination with paclitaxel in patients with advanced gastric (stomach) cancer or gastroesophageal junction (GEJ) adenocarcinoma were published in the online version of The Lancet Oncology.

In the trial, known as RAINBOW, the addition of ramucirumab to paclitaxel showed a statistically significant improvement in median overall survival, meeting its primary endpoint; it also met secondary endpoints of progression-free survival and objective response rate. 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.  Data from the RAINBOW trial were first presented at the Gastrointestinal Cancers Symposium (ASCO GI) in January 2014.

Ramucirumab has now been the focus of two positive Phase III gastric cancer trials that have demonstrated statistically significant improvements in both overall survival and progression-free survival. The first trial, REGARD, examined ramucirumab as a single-agent treatment for patients with advanced or metastatic gastric or GEJ adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. These study results were published in 2013.

"As the third leading cause of cancer death worldwide, stomach cancer is a major global health issue," said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. "We are encouraged by the RAINBOW study results and are pleased that we now have a second phase III trial of ramucirumab which has demonstrated improved survival in advanced gastric cancer patients."

RAINBOW was a global, randomised, double-blinded phase III study of ramucirumab and paclitaxel compared to placebo and paclitaxel as treatment in patients with advanced (locally advanced, unresectable or metastatic) gastric cancer or GEJ adenocarcinoma that was refractory to or progressive after initial platinum- and fluoropyrimidine-containing chemotherapy.

"I am very pleased that this trial demonstrated a significant and clinically meaningful benefit for patients with advanced stomach cancer," said Hansjochen Wilke, M.D., department of medical oncology, hematology with the Center for Palliative Care at Kliniken Essen-Mitte in Germany, and principal investigator of the RAINBOW trial. "Currently, there is a significant need for effective therapies to help combat this deadly disease and ramucirumab in this combination could provide a valuable second-line treatment option."

Patients randomised to the ramucirumab-plus-paclitaxel arm had a median survival benefit of 9.6 months, compared to 7.4 months for patients on the placebo-plus-paclitaxel arm (stratified hazard ratio 0.807 [95 per cent confidence interval (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 months vs. 2.9 months; stratified hazard ratio 0.635 [95 per cent 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).

The following adverse events (grade 3 or higher) occurred at a higher rate and for more than 10 percent of patients on the ramucirumab-plus-paclitaxel arm: neutropenia, or a decrease in a specific type of white blood cell (neutrophils) (41 per cent vs. 19 per cent); leukopenia, or decreased white blood cell count (all white blood cells) (17 per cent vs. 7 per cent); hypertension, or high blood pressure (15 per cent vs. 3 per cent); and fatigue/asthenia (12 per cent vs. 5 per cent). The incidence of febrile neutropenia, or a fever combined with decreased neutrophils, was low in both trial arms (3 per cent vs. 2 per cent, respectively).

Data from the RAINBOW trial are the basis for regulatory submissions in the US and EU; plans for a submission to Japanese regulatory authorities in the second half of 2014 are on track.