Safety Profile of Regorafenib in Treatment of Metastatic Colorectal Cancer
Posted: Monday, December 17, 2018
The safety profile of the multikinase inhibitor regorafenib was confirmed in a phase IIIb prospective, open-label, single-arm trial of patients with metastatic colorectal cancer whose disease progressed after standard therapy. The CONSIGN trial, which was built upon the results of the phase III CORRECT trial, reinforced the importance of modifying treatment to manage adverse events. These findings were published in The Oncologist by Eric Van Cutsem, MD, PhD, of the University Hospitals Leuven, Belgium, and his colleagues.
The trial followed 2,864 patients in 25 countries who had metastatic colorectal cancer and an Eastern Cooperative Oncology Group performance status of one or less. Patients were assessed after a median of three 4-week treatment cycles with regorafenib. About 75% of patients had received at least 3 prior regimens for metastatic disease before beginning the trial.
Treatment-emergent adverse events led to a dose reduction in 46% of patients and discontinuation of treatment in 9% of patients. Common treatment-emergent adverse events included hypertension (15%), hand-foot skin reaction (14%), fatigue (13%), diarrhea (5%), and hypophosphatemia (5%). Most fatal outcomes in the trial were determined to be related to disease progression, and less than 1% were thought to be related to the use of regorafenib.
Overall, the median progression-free survival was 2.7 months, and more than 23% of patients had a progression-free survival of more than 4 months.
“The rates of dose reductions and interruptions highlight the importance of optimal patient selection, dose modifications, and adverse event management during regorafenib treatment,” the investigators concluded.