Regorafenib Upped Survival in Asian Patients With Refractory mCRC

May 22, 2015

The CONCUR trial found that regorafenib improved overall survival in a large group of Asian patients with treatment-refractory metastatic colorectal cancer.

Regorafenib-an oral, small-molecule multikinase inhibitor-improved overall survival in a large group of Asian patients with treatment-refractory metastatic colorectal cancer compared with placebo, according to the results of the phase III CONCUR trial published in Lancet Oncology.

According to researcher Jin Li, MD, of the department of medical oncology at Fudan University Shanghai Cancer Center, China, and colleagues, this is the second phase III trial to show that regorafenib improves overall survival in this patient population, “substantiating the role of regorafenib as an important treatment option for patients whose disease has progressed after standard treatments.”

In the previously conducted CORRECT trial, regorafenib was found to improve overall survival  in patients with treatment-refractory disease compared with placebo plus best supportive care (hazard ratio [HR] = 0.77; 95% CI, 0.64–0.94).

In the phase III CONCUR trial, Li and colleagues wanted to evaluate regorafenib in a larger group of Asian patients. The researchers randomly assigned 204 patients recruited from 25 hospitals in China, Hong Kong, South Korea, Taiwan, and Vietnam to regorafenib (n = 136) or placebo (n = 68). Patients were followed for a median of 7.4 months.

After follow-up, patients assigned regorafenib had a 2.5-month improvement in overall survival compared with patients assigned placebo  (HR = 0.55; 95% CI, 0.40–0.77; P = .00016). In addition, patients assigned regorafenib also had significantly improved progression-free survival compared with placebo (HR = 0.31; 95% CI, 0.22–0.44; P < .0001). The median progression-free survival was 3.2 months for regorafenib compared with 1.7 months for placebo.

“In an exploratory analysis of the effect of previous targeted biological treatment, the HR for overall survival was 0.31 (95% CI 0.19–0.53) in favor of regorafenib in the 82 patients who had not previously received targeted treatment and 0.78 (0.51–1.19) in the 122 who had received at least one targeted biological drug,” the researchers wrote. “However, outcomes in some of the previous targeted treatment subgroups were confounded by the small number of patients (< 45) and imbalances in the proportion of patients receiving post-study treatments.”

Drug-related serious adverse events occurred in 9% of patients assigned regorafenib compared with 4% of patients assigned placebo. The most common grade 3 or worse adverse events related to the study drug were hand-foot syndrome (16%), hypertension (11%), hyperbilirubinemia (7%), hypophosphatemia (7%), alanine aminotransferase concentration increases (7%), aspartate aminotransferase concentration increases (6%), lipase concentration increases (4%), and maculopapular rash (4%).

In their discussion of the results, the researchers noted that the survival benefit seen in CONCUR was greater than that seen in CORRECT. They speculated that “the most likely reason is the difference in previous exposure to targeted treatments.”