Ramucirumab Takes Steps Forward in Gastric Cancer

Eli Lilly's VEGF receptor 2 inhibitor ramucirumab may offer a much-needed second-line treatment option for patients with advanced gastric or gastroesophageal junction cancer, according to results from the REGARD phase III clinical trial.

“Hopefully it's the beginning of a new phase of investigation that will really bring progress for patients with advanced stomach cancer,” says Charles Fuchs, MD, MPH, of Dana-Farber Cancer Institute in Boston, MA, who is lead investigator for the trial.

In the REGARD study, published in the Lancet in October, 238 patients randomized to receive the antiangiogenesis drug had a median overall survival time of 5.2 months, compared with 3.8 months for 177 patients given placebo. Ramucirumab was also associated with fewer toxic side effects than conventional treatment and with longer median progression-free survival (2.1 months versus 1.3 months for the placebo group).

“When we compare the results of this trial to trials in the same setting of chemotherapy versus best supportive care, the magnitude of benefit seems about the same, but what's encouraging is that the ramucirumab seems to have considerably less in the way of toxicity than what we experience with chemotherapy,” says Fuchs.

In September, Lilly disclosed top-line data from the RAINBOW phase III trial, which found statistically significant improved overall survival in patients with advanced gastric cancer treated with ramucirumab and paclitaxel compared to those who received placebo plus paclitaxel. (Lilly plans to present full details of the RAINBOW trial at a future scientific meeting.)

The results from the two trials “speak to a very relevant role for angiogenesis in stomach cancer, and hopefully lead to additional avenues of investigation,” says Fuchs.

The REGARD findings are exciting considering that prior trials of antiangiogenic agents have primarily shown benefit in combination with cytotoxic therapy, which cannot be tolerated by most patients with reduced performance status following primary treatment, says Roderich Schwarz, MD, PhD, medical director of Indiana University Health Goshen Center for Cancer Care and professor of surgery at the university's School of Medicine, both in South Bend.

In light of the REGARD and RAINBOW findings, future research should examine the use of antiangiogenic therapy for fully treated patients at high risk for recurrence of gastric cancer, says Schwarz.

Progression-free survival data from the REGARD trial also suggest that ramucirumab may be more effective in certain subgroups of patients. “We certainly hope to come up with a biomarker to individualize treatment a bit more appropriately,” he says.

“We want to look at using this antibody in earlier stages of stomach cancer and potentially with other targeted agents through pathways relevant to stomach cancer,” adds Fuchs.

Also in October, the U.S. Food and Drug Administration awarded Priority Review status to ramucirumab's marketing application for use as a monotherapy in advanced gastric cancer.