SAN ANTONIO – Adding the investigational antiangiogenesis agent ramucirumab to first-line chemotherapy did not significantly benefit metastatic breast cancer patients in a large phase III trial, Dr. John R. Mackey said at the San Antonio Breast Cancer Symposium.
The ROSE/TRIO-12 trial included 1,144 metastatic breast cancer patients in 25 countries who were randomized 2:1 to first-line docetaxel plus ramucirumab, a recombinant human IgG1 monoclonal antibody that binds to vascular endothelial growth factor receptor-2, or to docetaxel and placebo. After a median follow-up of 16.2 months, investigator-assessed progression-free survival was 9.5 months in the ramucirumab group and was not significantly different at 8.2 months in controls. No clinically defined subgroup showed a benefit with combination therapy, reported Dr. Mackey, professor of oncology at the University of Alberta, Edmonton, and director of Translational Research in Oncology (TRIO), which conducted the trial.
Dr. Peter Ravdin
Median overall survival was 27.3 months with ramucirumab and 27.2 months in controls. However, the overall response rate, disease control rate, and time to progression were greater in the combined therapy group.
"We’re hopeful that we can go back to the tissue samples and find predictive biomarkers because there is a signal here. We are seeing improvements in several endpoints and some patients clearly are benefiting, but we do not understand the biology sufficiently well to be able to pick them out of the general population," he said.
Dr. Mackey noted that ramucirumab is the focus of a broad phase III clinical trial program. Definitive phase III studies of the antiangiogenesis agent in lung and colon cancer are underway. And two phase III trials in gastric cancer – REGARD and RAINBOW – have been completed with positive results for overall survival. "I think we can say that at least in another disease setting, this agent has activity."
Despite the negative results in ROSE/TRIO-12 plus the negative outcomes for trials of bevacizumab (Avastin), this is not the end of the line for antiangiogenesis agents in breast cancer, said conference codirector Dr. Peter Ravdin of the University of Texas, San Antonio. "Breast cancer is a really diverse disease. Drugs that may on average have little value in breast cancer may be very effective in selected populations."
The ROSE study was funded by Eli Lilly. Dr. Mackey declared having no financial conflicts of interest.