According to results from a new clinical trial, an experimental cancer drug regorafenib appears to extend survival slightly in patients with metastatic colorectal cancer. Regorafenib is a so-called multikinase inhibitor, which targets several of the ways cancer develops and grows, researchers said.
“The drug was tested on patients with metastatic colorectal cancer who had progressed after standard therapies, meaning they had no treatment options available,” lead researcher Dr. Axel Grothey, a professor of oncology at the Mayo Clinic, said during a press conference at the Gastrointestinal Cancers Symposium in San Francisco on Tuesday. The drug is designed to stop tumor progression, both by preventing cancer cells from growing and by preventing these cells from developing the blood vessels needed to keep them alive, the researchers explained.
The CORRECT trial was conducted to evaluate the efficacy and safety of regorafenib in patients with metastatic disease who had progressed after receiving all approved standard therapies. The clinical trial included more than 700 patients with metastatic colon cancer who were randomly selected to receive regorafenib or placebo. In addition, all patients received care to treat symptoms, but not to change the course of the disease, the researchers noted. Treatment included antibiotics to fight infections, painkillers and corticosteroids.
Results showed that patients taking regorafenib survived an average of 6.4 months, compared with five months for those receiving a placebo -- an increase in survival of 29 percent. In addition, 44 percent of the patients taking regorafenib responded to the drug or had their cancer slowed, compared with 15 percent of the patients receiving placebo, they reported. Based on these findings, the trial was stopped in October so that all patients could be offered the drug. The trial was funded by the maker of regorafenib, Bayer HealthCare Pharmaceuticals.
“The drug helped patients live longer,” said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society. “But you have to keep in mind that these patients had advanced disease.” And, the gains were modest, he added. “Patients who got the drug lived about one month longer. Unfortunately, the difference between the groups in the time it took for the disease to get worse was small - about six days,” he said. Lichtenfeld thinks that using the drug earlier in treatment might have more impact. “But not every drug, when moved earlier in the course of the disease, is necessarily proven to be effective,” he cautioned.
Adverse events were consistent with observations from previous clinical trials, said Dr. Grothey. Dose adjustment was helpful in managing adverse effects; “most patients could continue on the drug in a dose-reduced manner,” he explained. The most frequent adverse events in the regorafenib group were hand–foot skin reaction (17%), fatigue (15%), diarrhea (8%), hyperbilirubinemia (8%), and hypertension (7%).
Dr. Grothey noted that regorafenib appears to be more effective in stabilizing disease and delaying progression than in shrinking tumors. He added that a subset of patients has responded particularly well to regorafenib and continue to have stable disease. He said that he is personally treating a patient who has been on the drug for 12 months whose disease has stabilized and who has not experienced any adverse effects. “This is the first small-molecule kinase inhibitor with proof of efficacy in metastatic colorectal cancer,” he said, adding that this is a potential new standard of care in this patient population.
Grothey noted regorafenib is being tested in a phase 2 trial in patients with earlier stage colorectal cancer, in hopes that the results will be even more dramatic. Bayer HealthCare, the makers of regorafenib, said it would seek Food and Drug Administration approval of the medication this year. If approved, regorafenib would be the first new treatment for colorectal cancer in more than five years.
This is a very noteworthy study, said Morton Kahlenberg, from the University of Texas Health Science Center at San Antonio, who moderated the presscast. He added that these are positive findings in people with disease that has already progressed and who have failed other therapies. “This really lays the groundwork for further work,” he added.
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