REGARD VEGF receptor-2 as gastric cancer target

Oct 22 2013

By Lynda Williams, Senior medwireNews Reporter

Targeting vascular endothelial growth factor (VEGF) receptor-2 mediated signaling is an effective strategy against advanced gastric cancer, results from the REGARD trial demonstrate.

“Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy,” report Charles Fuchs (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and co-investigators.

Overall, 355 patients in North, Central and South America, Europe, Asia, Australia, and Africa were randomly assigned to receive the monoclonal antibody VEGF receptor-2 antagonist ramucirumab (8 mg/kg, n=238) or placebo (n=117) at 2-week intervals.

Median overall survival was significantly longer in patients given ramucirumab than those given placebo, at 5.2 versus 3.8 months and a significant hazard ratio of 0.78, the team reports in The Lancet.

Moreover, the survival benefit with ramucirumab did not significantly change after adjusting for three factors significantly linked with survival: Eastern Cooperative Oncology Group performance status, primary tumor location, and peritoneal metastases.

Ramucirumab treatment also conferred a 52% reduction in the risk for disease progression and all-cause mortality, with median progression-free survival of 2.1 months compared with 1.3 months in controls.

At time of data cutoff, treatment had been discontinued by 93% of ramucirumab-treated patients and 97% of controls, with a similar overall rate of adverse events (94 vs 88%) and deaths related to study drug (2 vs 2%), except for a significantly higher rate of hypertension with the monoclonal antibody therapy (16 vs 8%).“[T]his novel drug has a mechanism of action and toxic-effect profile that is distinctly different and non-overlapping with standard chemotherapy for oesophagogastric adenocarcinoma,” write Fuchs et al.

They say: “Future analyses are needed to identify potential predictive biomarkers for ramucirumab.”

In an accompanying comment, David Ilson (Memorial Sloan-Kettering Cancer Center, New York, USA) calls the REGARD results a “landmark in the treatment for gastric cancer,” noting that ramucirumab is the first anti-angiogenesis agent to produce a survival benefit in the disease and has potentially less damaging side effects than conventional chemotherapy.

While acknowledging that REGARD participants may not be typical advanced gastric cancer patients due to their high functional status and normal organ function, he nevertheless concludes: “We now await with anticipation reporting of the ongoing trials of ramucirumab combined with chemotherapy in early lines of therapy.”

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