Experimental Drug Improves Survival in Previously Treated Metastatic Colorectal Cancer ► NCI Cancer Bulletin for January 24, 2012 - National Cancer Institute

NCI Cancer Bulletin for January 24, 2012 - National Cancer Institute

Experimental Drug Improves Survival in Previously Treated Metastatic Colorectal Cancer

Treatment with the investigational agent regorafenib modestly improved survival for patients with metastatic colorectal cancer whose disease had progressed after multiple prior treatments, according to clinical trial results presented last week at the 2012 Gastrointestinal Cancers Symposium.

The trial’s Data and Safety Monitoring Committee stopped the trial after a preplanned interim analysis showed a 1.4-month improvement in median overall survival, said the trial’s lead investigator, Dr. Axel Grothey of the Mayo Clinic Cancer Center in Minneapolis.

In the trial, called CORRECT, 760 patients were randomly assigned to receive regorafenib in combination with best supportive care—that is, care designed to treat symptoms but not to cure the underlying disease—or a placebo and best supportive care. Regorafenib, which comes in pill form, targets several specific enzymes known as kinases that regulate key tumor cell processes, including cell growth and proliferation.

The median overall survival was 6.4 months for patients who received regorafenib and 5 months for patients who received the placebo. After the randomized phase of the trial was stopped, patients in the placebo arm could choose to cross over and receive regorafenib.

Approximately two-thirds of the patients in the trial had received at least four prior treatments. Common side effects of regorafenib included skin rash, fatigue, diarrhea, and hypertension, which could be managed with medications and dose reductions, Dr. Grothey explained.

Fewer than 2 percent of the patients who received regorafenib experienced significant tumor shrinkage. But 44 percent of patients who received regorafenib had no measurable tumor growth or worsening of symptoms compared with 15 percent of patients treated with placebo.

Unlike many chemotherapy drugs and targeted agents, which are cytotoxic—that is, they kill cancer cells—regorafenib appears to be primarily cytostatic, meaning it arrests tumor growth, Dr. Grothey noted.

Other primarily cytostatic agents are in development. Traditional measures of treatment efficacy, such as tumor shrinkage, will have to be reconsidered, Dr. Grothey noted, or “we might miss agents that are cytostatic” and can help control tumor growth and progression.

Last year the Food and Drug Administration granted regorafenib, which is manufactured by Bayer, “fast track” designation for the treatment of patients with metastatic colorectal cancer whose disease has progressed despite multiple treatments with FDA-approved drugs. The fast-track process is designed to expedite the agency’s review of treatments for diseases with unmet needs.