Regorafenib promising for advanced gastric adenocarcinoma

Last Updated: 2016-06-29

By Marilynn Larkin

NEW YORK (Reuters Health) - Regorafenib may delay cancer progression in patients with refractory advanced gastric adenocarcinoma, according to a phase 2 trial.

The compound, developed by Bayer, the study's sponsor, is an inhibitor of multiple kinases and is approved in the U.S. for the treatment of certain patients with metastatic colorectal cancer or metastatic gastrointestinal tumor.

For the trial, called INTEGRATE (Randomized phase II double-blind placebo-controlled study of Regorafenib refractory advanced esopgago-gastric cancer), Dr. Nick Pavlakis of the University of Sydney, Australia, and colleagues evaluated the drug's activity in advanced gastric carcinoma.

The team randomly assigned 97 patients to oral regorafenib 160 mg and 50 patients to oral placebo on days one to 21 of each 28-day cycle until disease progression or prohibitive adverse events occurred, they write in the Journal of Clinical Oncology, online June 20.

The median duration of active treatment was 1.8 months for regorafenib and 0.9 months for placebo. Median progression-free survival differed significantly between the groups, with 2.6 months for regorafenib and 0.9 months for placebo (hazard ratio, 0.40; p<0.001).

The effect was greater for patients in South Korea than in Australia, New Zealand, and Canada combined but consistent across age, neutrophil-to-lymphocyte ratio, primary site, lines of chemotherapy, number of metastatic sites, and other measures.

The team also found a survival trend in favor of regorafenib (median, 5.8 months vs. 4.5 months; HR, 0.74; p=0.147).

Dr. Pavlakis told Reuters Health by email, "The INTEGRATE study confirmed the promising activity and safety of regorafenib in patients with advanced/refractory gastric cancer. It is being followed by an international multicenter Phase III trial that I am co-chairing, co-ordinated by the Australasian Gastrointestinal Trials Group, involving sites in Australia, New Zealand, Korea, Japan, Taiwan, Canada and USA."

"The INTEGRATE II is expected to commence recruitment late in the third quarter of 2016," added Dr. Pavlakis, who along with several co-authors reported financial ties to Bayer.

Dr. Yelena Janjigian, a specialist in esophageal and stomach cancers at Memorial Sloan Kettering Cancer Center in New York City, told Reuters Health by phone that she is "cautiously optimistic."

"This is a phase II trial comparing against placebo, so while it's reassuring, we have to see what happens in phase 3, keeping in mind that the drug can be quite toxic in patients," she said.

She suggested that the regional differences in outcomes "point to differences in the biology of this cancer in East versus West."

SOURCE: http://bit.ly/2951a84

J Clin Oncol 2016.