CONSIGN, CONCUR Confirm Efficacy of Regorafenib in mCRC

Two phase III trials have confirmed the benefit of regorafenib, an oral multikinase inhibitor, in patients with previously treated metastatic colorectal cancer.

The results of two phase III trials have confirmed the benefit of regorafenib, an oral multikinase inhibitor, in patients with previously treated metastatic colorectal cancer (mCRC).

At the ESMO World Congress on Gastrointestinal Cancer 2015 in Barcelona, researchers presented updated results of the CONSIGN study (abstract LBA-05), which was designed to allow patients with metastatic disease access to the drug before marketing approval and to assess safety, and the CONCUR study (abstract O-0011), which evaluated the use of the drug in Asian patients.

Regorafenib was given regulatory approval based on the results of the CORRECT study, which showed the drug significantly improved survival compared with placebo in patients with previously treated mCRC.


The CONSIGN trial was a prospective, open-label study that included 2,872 patients who had progressed after standard therapies and had an ECOG performance status of 0 or 1. Patients were assigned regorafenib 150 mg once daily for the first 3 weeks of each 4-week cycle. Patients received the drug for a median of 2.5 months.

“We began CONSIGN at the suggestion of the authorities and to fulfill the wishes of patients and doctors for a larger expanded access,” said lead study author Eric Van Cutsem, MD, PhD, of the University Hospitals Leuven, Belgium, in a prepared statement.

Grade 3 or worse adverse events occurred in 80% of patients. The estimated progression-free survival was 2.7 months and was similar in patients regardless of KRAS gene status.

“CONSIGN depicts what we would expect from an observational trial in this setting,” said Dirk Arnold, MD, ESMO spokesperson, director of the department of medical oncology, Klinik für Tumorbiologie in Freiburg, Germany, in a prepared statement. “It shows that we have further treatment options for mCRC patients pretreated with chemotherapy, and that this comes at the cost of a specific, but manageable toxicity profile.”


In the CONCUR trial, patient enrollment was limited only to Asian patients. Included patients were not required to have had prior treatment with a biologic targeted therapy.

The researchers randomly assigned 204 patients 2:1 to regorafenib 160 mg or placebo for the first 3 weeks of an every 4-week cycle.  According to the study, patients in CONCUR had fewer treatment lines for metastatic disease, a higher proportion of patients had a performance status of 1, and 40% had no prior biologic targeted therapy.

Median overall survival was 8.8 months for patients treated with regorafenib compared with 6.3 months for placebo (P = .0002). In CORRECT, the median overall survival was 6.4 months compared with 5 for placebo (P = .0052). These patients also saw significant improvements in progression-free survival (3.2 months vs 1.7 months; P < .0001).

Commenting on the data, Arnold said: “Patients in the CORRECT trial were more heavily pretreated than patients in the CONCUR trial. For example, all patients in CORRECT had pretreatment with anti-VEGF and about 50% had pretreatment with an anti-EGFR. In the CONCUR trial about 60% of patients had pretreatment with any of these two compounds, and 40% were not pretreated with a targeted biological treatment.”

He continued: “The differences in pretreatment may be responsible for the better outcome of patients getting active treatment in the CONCUR trial compared to the CORRECT trial. The hypothesis could be made that less pretreatment allows a larger gain of overall survival by adding a drug like regorafenib in this setting.”