The Phase IIIb CONSIGN study has confirmed the benefit of regorafenib in patients with previously treated metastatic colorectal cancer (mCRC).

Researchers announced the results at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2015 in Barcelona

The safety profile and progression free survival were similar to Phase III trial results.

CONSIGN was a prospective, observational study that was initiated to allow patients with mCRC access to regorafenib before marketing authorisation and to assess safety, which was the primary endpoint. The randomised Phase III CORRECT trial previously showed that regorafenib significantly improves survival in patients with pre-treated mCRC and led to regulatory approval.

“We began CONSIGN at the suggestion of the authorities and to fulfil the wishes of patients and doctors for a larger expanded access,” said lead study author Prof Eric Van Cutsem from University Hospitals Leuven, Belgium. “Today we report on safety and progression-free survival in a large cohort of patients that more closely resembles daily clinical practice than the pivotal registration trial.”

CONSIGN included more than 2,800 patients at 188 sites in 25 countries who received regorafenib for a median of 2.5 months. Grade >3 adverse events occurred in 80% of patients. The estimated progression-free survival was 2.7 months and was similar across KRAS wild type and mutant subgroups.

Need to establish guidelines on the management of adverse events to make regorafenib more tolerable for patients

Van Cutsem said, “This study in a real world population of patients with pre-treated mCRC shows a similar safety profile and progression-free survival with regorafenib as shown in the randomised CORRECT trial. The findings add to our knowledge of how to select patients and how to manage toxicities. We need to establish clear guidelines on the management of adverse events to make taking the drug more tolerable for patients.”

Commenting on the data, Dr Dirk Arnold, ESMO spokesperson, director of the Department of Medical Oncology, Klinik für Tumorbiologie in Freiburg, Germany, said, “CONSIGN confirms the efficacy and safety data of the randomised Phase III CORRECT and CONCUR trials. The merit of CONSIGN is that it translates Phase III data into the clinical routine since patients had similar characteristics and pre-treatment to what we see in daily practice.”

The adverse events reported in CONSIGN were within the scope of expectation and comparable to the CORRECT trial, added Arnold. “There were no surprising findings in terms of toxicity,” he said. “All of the adverse events were quite class specific and also likely manageable.”

He added, “CONSIGN depicts what we would expect from an observational trial in this setting. It shows that we have further treatment options for mCRC patients pre-treated with chemotherapy, and that this comes at the cost of a specific, but manageable toxicity profile.”

Regarding the next step in this research area, Arnold said, “Biomarkers have been extensively investigated in the randomised trials but until now nothing has been found that would allow prediction of the benefit of regorafenib for a specific group of patients. I would suggest having a further look at the data in the observational CONSIGN study to see if there are clinical characteristics that identify patients who could benefit more or less from this treatment.”

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