CONCUR: Regorafenib Active in Asian Patients

In the CONCUR trial of 204 patients, reported by Jin Li, MD, Professor and Director of the Department of Medical Oncology at Fudan University Shanghai Cancer Center, use of regorafenib—an oral multikinase inhibitor that targets pathways involved in tumor growth and progression—was associated with a 45 percent reduction in the risk of death in Asian patients with metastatic colorectal cancer who had disease progression after standard therapy compared with placebo. And approximately half of treated patients experienced a clinical response or stable disease.

CONCUR, which was sponsored by Bayer HealthCare Pharmaceuticals, met its response goals but not the toxicity goals. “Regorafenib needs dose and schedule refinement,” Goldberg said in his discussion of the trial, suggesting dose reductions or a one-week-on one-week-off strategy.

With a median of 10.6 weeks under treatment, about 26 percent of patients had dose reductions and 66 percent had dose interruptions. “The biggest challenge for regorafenib researchers is to find a better way to give this drug so we can exploit its benefit, because there was a relatively high rate of grade 3 and 4 toxicity,” he said. “For those of us who use regorafenib in the clinic, treatment tolerance is the biggest issue we face.”

JIN LI, MD. JIN LI.

RICHARD M. GOLDBERG.

But only 15 percent of patients enrolled in CORRECT were Asian—mostly from Japan—while all patients in CONCUR were from mainland China, Hong Kong, Taiwan, the Republic of Korea, and Vietnam.

Patients who had disease progression after at least two prior lines of standard therapy were randomly assigned to receive oral regorafenib (136 patients) or placebo (68 patients) for the first three weeks of a four-week cycle. Prior anti-VEGF or anti-EGFR was allowed but not required.

The most frequent treatment-emergent adverse effects were hand-foot skin reaction (16% of patients), hypertension (12%), hyperbilirubinemia (12%), elevated liver enzymes (AST 10%, ALT 8%), hypophosphatemia (9%), anemia (7%), and hyperlipasemia (7%). There were no reports of liver failure or pancreatitis.

“What is important [regarding serious adverse events] is that the rate with regorafenib was similar to that of placebo—31.3 percent and 26.5 percent, respectively,” Li said.