The results of the CORRECT trial created some degree of “buzz” at the 2012 Gastrointestinal Cancers Symposium, with experts predicting that regorafenib will become FDA-approved and have strong clinical utility. While numerically, the benefit appeared small, “There is a real difference with this drug,” maintained Richard Goldberg, MD, of Ohio State University Medical Center, Columbus, who chaired the meeting’s steering committee.

“I certainly hope it will be approved,” he said in an interview. “Many of my patients run out of effective options for treatment long before they are ready to make a transition to supportive care alone.”

Dr. Goldberg observed that the magnitude of benefit is similar to what was initially observed with cetuximab (Erbitux) and panitumumab (Vectibix) prior to the identification of KRAS as a biomarker. Finding such a biomarker for multikinase inhibitors such as regorafenib will be important, he noted.

Search for New Therapies

Herbert Hurwitz, MD, of Duke Cancer Institute in Durham, North Carolina, the invited discussant of Dr. Goldberg's presentation, said that the findings “credential” vascular endothelial growth factor (VEGF) as a useful target in colorectal cancer, but suggested that researchers “move beyond” VEGF and epidermal growth factor receptor in their search for new therapeutic options.

“Why did this drug work?” he asked. One reason may lie in the pharmacokinetics. While regorafenib and sorafenib (Nexavar) are “close cousins,” the M5 metabolite of regorafenib has a prolonged half-life (about 3 days), which may allow for target coverage during the week in which patients are off the drug. Also helping to show a treatment effect was the “clean design” of the study—single agent, no crossover, he added.

“This is the first study that is a clean, randomized, monotherapy comparison to best supportive care, and I applaud the investigators for this,” he said.

Further Investigation

Like Dr. Goldberg, Dr. Hurwitz maintained that the overall and progression-free survival benefits were “clinically meaningful for many patients,” though he believes toxicity, especially hand-foot reactions, could be a concern for some. “This merits further investigation since these reactions can affect quality of life and occasionally lead to discontinuations.”

While regorafenib is a strong candidate for regulatory approval, he said, it is important to determine the drug’s value in patients with poor performance status (who were not included in CORRECT), and its activity when given on a weekly, continuous basis. ■

Disclosure: Dr. Goldberg has received research support (which goes to Ohio State University) from Bayer. Dr. Hurwitz reported no potential conflicts of interest.