New research conducted at the University of Texas MD Anderson Cancer Center concluded that combining vermurafenib, cetiximab and irinotecan in the treatment of patients diagnosed with advanced colorectal cancer, an aggressive, poor-responsive disease, brought satisfactory responses in study participants.
The Phase I trial, which was presented on Saturday, May 31st in a poster discussion at the American Society of Clinical Oncology’s 2014 Annual Meeting in Chicago, explores a specific mutation in the BRAF gene, present in 5 to 10 percent of colorectal cancer patients.
The need to target this mutation in therapy had been previously identified, but using vemurafenib singly in previous studies was not very effective, making researchers consider combining it with other drugs.
A BRAF mutation in this form of cancer is “an aggressive disease that doesn’t typically respond to standard chemotherapy,” explains David Hong, M.D., an associate professor at Investigational Cancer Therapeutics and lead author of the study. He added that “when BRAF inhibitors initially started, there was excitement this could become the new standard of care, however we found they didn’t work very well.”
For the new trial, researchers decided to use escalating doses of vermurafenib (V), combined with both cetuximab and irinotecan (I), also used previously for treating metastatic colorectal cancer.
The study involved twelve patients divided into two groups. Seven patients received dose level one (V-480 mg, C-250 mg and I-180 mg) and five were administered dose level two, in which the vemurafenib dose was increased to 720 mg.
The treatment consisted of a 14-day cycle, evaluated every four cycles through radiographic images.
Nine patients were deemed evaluable, and partial responses or stable disease were observed in eight of them. After beginning their treatment, they had gone through restaging scans. The less than 10 percent response rate in patients treated with single-agent vemurafenib raised to 50 percent in the eight colorectal patients.
“What’s promising is the fact that we’re seeing these high response rates in early studies which suggests this could become a new standard of care down the line,” Hong explained. “There’s clearly some kind of synergistic activity with the combination.”
Scott Kopetz, M.D., Ph.D. in Gastrointestinal Medical Oncology, senior author of the Phase I study, will lead a U.S. cooperative randomized Phase II trial of this combination of drugs in BRAF-mutated colorectal cancer, beginning later this summer.
“While early, the exciting aspect is that we’re seeing substantial response rates, but questions remain about the duration of these responses and what the mechanisms of resistance are,” Kopetz said. “By expanding on our initial findings and moving to the cooperative group network we’ll be able to rapidly perform studies that could lead to getting this combination approved.”