An international phase III trial presented at ASCO's ninth annual Gastrointestinal Cancers Symposium shows that single-agent treatment with the investigational drug regorafenib significantly improves survival and delays cancer progression in patients with metastatic colorectal cancer that has progressed despite other approved treatments, as compared to treatment with placebo and supportive care. Regorafenib is a novel, oral agent that targets multiple biological pathways involved in cancer development and growth.

"When standard therapies for patients with metastatic colorectal cancer stop working, and the cancer continues to worsen, most patients only survive a few months," said lead author Axel Grothey, M.D., professor of oncology at the Mayo Clinic in Rochester, MN. "So it's exciting that this is the first time an agent has shown a statistically significant overall survival benefit, in some cases adding many more months of life, in these patients in a randomized phase III study."

Regorafenib inhibits a number of pathways involved in tumor progression, including those involved in cell proliferation and angiogenesis. These may include VEGFR, PDGFR-beta, and KIT, among others.

The trial, called CORRECT, was a randomized phase III study of patients whose metastatic colorectal cancer progressed despite standard treatments. In the trial, 760 patients from 105 centers were randomized to receive best supportive care plus either regorafenib or placebo. Best supportive care involves treatment to address the symptoms of cancer, rather than to improve the overall disease outcomes; it includes therapies such as antibiotics, analgesics, radiation therapy for pain from bone metastases, and corticosteroids.

At the second interim data analysis, the researchers found that the median overall survival was 6.4 months for regorafenib and 5.0 months for placebo – a 29 percent increase in overall survival. They also found a substantial difference in disease control rate (DCR): 44 percent in the regorafenib group versus 15 percent for placebo. DCR is defined as the percentage of patients who have a partial or complete response to a drug, or stable disease.

"Tumors that progress after first-, second- and even third-line treatment have developed elaborate mechanisms and pathways that enable them to resist chemotherapy and sustain their growth. Using a multitargeted drug alone, without chemotherapy, is a novel approach for overcoming some of the tumor's defenses and sparing patients the side effects of additional chemotherapy," Grothey said.

According to Grothey, regorafenib appears more effective in stabilizing disease and delaying tumor growth, rather than in shrinking tumors. He said that a subset of patients in the trial have responded particularly well to regorafenib, continuing to have stable disease for a relatively long time; research is ongoing to find ways to identify these individuals. "The current era in oncology is about individualizing therapy and not treat every patient the same way," he said. "We'd like to find biomarkers that could tell us exactly which patients will likely benefit from treatment with regorafenib.