Flexible Regorafenib Dosing Shows Promise as Alternative Therapy for Metastatic CRC

Barcelona, Spain—Flexible regorafenib dosing is promising as an alternative therapy option for patients with metastatic colorectal cancer (CRC), according to results from the REARRANGE trial presented for the first time at the ESMO 21st World Congress on Gastrointestinal Cancer.

“Regorafenib improves overall survival compared with placebo in patients with refractory, metastatic colorectal cancer. However, regorafinib’s adverse tolerability has jeopardized its implementation in clinical practice,” explained Guillem Argilés, MD, Department of Medical Oncology, Vall d’Hebron Institute of Oncology, Barcelona, Spain, during his presentation.

A total of 299 patients with refractory, metastatic CRC were randomized 1:1:1 to receive regorafenib at the standard dose (SD) of 160 mg daily 3 weeks on and 1 week off, reduced dose (RD) of 120 mg daily 3 weeks on and 1 week off, or intermittent dose (ID) of 160 mg 1 week on and 1 week off.

Patients receiving RD or ID were escalated to SD following 1 cycle of treatment so long as no limiting toxicities occurred.

The primary endpoint was safety: the percentage of patients with grade 3/4 treatment-related adverse events. Secondary end points were OS, progression-free survival, dose intensity, and tolerability.

The trial positivity threshold was based on a 20% decrease in the percentage of patients with grade 3/4 adverse events receiving RD or ID versus SD.

With SD, RD, and ID, the safety population set was 100, 98, and 99, respectively, and the median treatment duration was 3.2 months, 3.7 months, and 3.8 months. PFS did not differ across the 3 group and was approximately 2 months.

There were 60%, 56%, and 55% of patients with grade 3/4 adverse events with SD, RD, and ID, respectively. In the RD and ID arms, 45% and 64% of patients were escalated to SD after cycle 1.

“Though REARRANGE did not meet its primary endpoint of improving [regorafenib] global tolerability in either RD or ID arms, flexible dosing showed numerical improvement on relevant [adverse events] like fatigue…and hypertension, without jeopardizing efficacy,” Dr Argilés and colleagues reported.

“These findings support the use of [regorafenib] flexible dosing as an alternative option,” they concluded.—Hina Khaliq

Argilés G, Mulet Margalef N, Valladares-Ayerbes M, et al. Results of REARRANGE trial: A randomized phase 2 study comparing different dosing approaches for regorafenib (REG) during the first cycle of treatment in patients (pts) with metastatic colorectal cancer (mCRC). Presented at: the ESMO 21st World Congress on Gastrointestinal Cancer; July 3-6, 2019; Barcelona, Spain. Abstract O-026.