In patients from the United States enrolled in the phase 3b CONSIGN trial, the safety profile of regorafenib was consistent with that of the overall study population and the known safety profile of regorafenib in patients with metastatic colorectal cancer (mCRC), according to findings presented at the 2016 Gastrointestinal Cancers Symposium in San Francisco, CA.1

CONSIGN was a large, international, open-label, single-arm trial that evaluated regorafenib in 2872 patients with mCRC who failed standard therapy. The patients were from 25 countries.

The study was designed to provide continued access to regorafenib and to further characterize the safety of the oral multi-targeted kinase inhibitor. Participants received regorafenib 160 mg orally daily for the first 3 weeks of each 4-week cycle until disease progression or unacceptable toxicity.

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Now, researchers are reporting results from a retrospective subgroup analysis of patients enrolled in CONSIGN in the United States.

Of the evaluable 2864 patients, 364 were treated in the United States. The median age of these patients was 60 years and 38% and 62% had an Eastern Cooperative Oncology Group performance status of 0 and 1, respectively.

Results showed that grade 3 or worse treatment-emergent adverse events occurred in 53% of patients in the US and 57% of the overall study population. Researchers found that grade 3 or worse hepatobiliary disorders were reported in 2% of the US cohort with elevated bilirubin, AST, and ALT occurring in 9%, 6%, and 3%, respectively.

Of note, serious treatment-related adverse events occurred in 7% of patients in the United States and 9% of all patients, and 8% and 9%, respectively, experienced adverse events leading to treatment discontinuation.

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In regard to efficacy, median progression-free survival (2.3 months; 95% CI, 2.0 – 2.6) in the US cohort was also in the range of that reported in phase 3 trials.


  1. Verma U, Arriaga YE, Lenz H-J, et al. Regorafenib for previously treated metastatic colorectal cancer (mCRC): A subgroup analysis of 364 patients in the USA treated in the international, open-label phase IIIb CONSIGN study. J Clin Oncol. 2016;34 (suppl 4S; abstr 735).