Regorafenib is often administered to patients with refractory metastatic colorectal cancer. However, some of the adverse events related to the use of this drug often limit its use in clinical practice. A study reported by Argilés et al at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2019 suggests the usefulness of more flexible dosing, which can improve patients’ quality of life without jeopardizing efficacy (Abstract O-026).
“Regorafenib has been approved since 2013 for patients with metastatic colorectal cancer [whose disease has] progressed [on] standard treatments,” said first study author Guillem Argilés, MD, a medical oncologist and clinical investigator in the Gastrointestinal & Endocrine Tumors Group at Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology. “Its adverse toxicity profile often limits its use in routine clinical practice. This clinical trial attempted to show the usefulness of different dose strategies in order to improve its tolerability and quality of life in patients who can benefit from the medicine in the context of advanced disease.”
REARRANGE Trial Methods
The international REARRANGE trial, led by the Spanish Cooperative Group for the Treatment of Digestive Tumours, included 299 patients from over a dozen hospitals in Spain, Italy, and France. The average age of participants was 64 years, and they had received an average of four treatment lines prior to inclusion in the trial with regorafenib between July 2016 and September 2017.
In the trial, patients were randomly assigned 1:1:1 to either a standard dose of regorafenib—160 mg/d for 3 weeks followed by 1 week off; a reduced dose of 120 mg/d for 3 weeks followed by 1 week off (reduced-dose group); or an intermittent dose of 160 mg/d for 1 week, followed by 1 week off (intermittent-dose group). The patients in the latter two groups were escalated to the standard-of-care dose if, after a first treatment cycle, no limiting toxicities occurred.
“We reduced the dose in the first cycle and then escalated it because it has been shown that the toxicity is higher in the first and second months of treatment,” explained Dr. Argilés.
The investigators observed that flexible dosing showed numeric improvement on several parameters that increased tolerance, such as fatigue, hypertension, or hand-foot syndrome. However, REARRANGE did not meet its primary endpoint of improving regorafenib global tolerability in the reduced- and intermittent-dose groups.
The average treatment duration was 3.2 months in the standard group, 3.7 months in the reduced-dose group, and 3.8 months in the intermittent-dose group. Median progression-free survival was not different across groups (approximately 2 months).
“Although statistical significance was not achieved, we did observe a numeric reduction in some side effects that can be very troublesome for patients,” explained Dr. Argilés. “These results, interpreted in the context of other trials, like the American study ReDOS, tell us that the more flexible doses of regorafenib are an effective alternative in order to improve quality of life in patients with metastatic refractory colorectal cancer.”
Commenting on the results, Eric Van Cutsem, MD, PhD, of University Hospitals Leuven, said, “This study will change clinical practice with regard to the use of regorafenib in patients with metastatic colorectal cancer, because it demonstrates and supports something that many clinicians have already observed and were carrying out in regular clinical practice.”
Disclosure: For full disclosures of the study authors, visit academic.oup.com.
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