ESMO World GI 2015: Studies Confirm Regorafenib Benefit in Pretreated Metastatic Colorectal Cancer


Key Points

  • The CONSIGN trial confirmed the data of two previous studies, CORRECT and CONCUR, regarding the benefit of regorafenib in patients with metastatic colorectal cancer.
  • Researchers hope to further identify biomarkers that could help classify which patients may benefit the most from regorafenib treatment.
  • Types of pretreatment (anti-VEGF, anti-EGFR, combination of compounds, no biologic treatment) also alter the efficacy of regorafenib.

The phase IIIb CONSIGN trial has confirmed the benefit of regorafenib (Stivarga) in patients with previously treated metastatic colorectal cancer, researchers announced July 3 at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer in Barcelona, Spain (Abstract LBA-05). The safety profile and progression free survival were similar to those in phase III trial results.

CONSIGN was a prospective, observational study that was initiated to allow patients with metastatic colorectal cancer access to regorafenib before marketing authorization to assess safety. The randomized phase III CORRECT trial previously showed that regorafenib significantly improved survival in patients with pretreated metastatic colorectal cancer and led to regulatory approval.

Lead author Eric Van Cutsem, MD, PhD, Head of the Department of Clinical Digestive Oncology at University Hospitals Leuven in Leuven, Belgium, said, “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 that 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.

Dr. Van Cutsem said, “This study in a real world population of patients with pretreated metastatic colorectal cancer shows a similar safety profile and progression-free survival with regorafenib as shown in the randomized 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, Dirk Arnold, MD, ESMO Spokesperson and Director of the Department of Medical Oncology at Klinik für Tumorbiologie in Freiburg, Germany, said, “CONSIGN confirms the efficacy and safety data of the randomized 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 pretreatment 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 Dr. Arnold. “There were no surprising findings in terms of toxicity,” he said. “All of the adverse events were quite class-specific and 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 metastatic colorectal cancer patients pretreated with chemotherapy and that this comes at the cost of a specific, but manageable, toxicity profile.”

Regarding the next step in this research area, Dr. Arnold said, “Biomarkers have been extensively investigated in the randomized 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.”


Another analysis presented July 3 (Abstract O-0011) discussed the characteristics and outcomes of patients in the CONCUR and CORRECT trials. The analysis confirmed overall survival improved in Asian and non-Asian patients, and adverse events were similar across the two trials.

Commenting on the data, Dr. 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.”

Dr. Arnold concluded, “The main difference between the two trials is that all patients in CONCUR were of Asian origin, whereas only 15% of patients had an Asian background in CORRECT. It's not clear whether it is ethnicity or pretreatment that brings the difference in benefit, but very likely, it's the pretreatment.”

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