The pivotal study was Study 14387 (CORRECT study), a randomised double blind, placebo controlled, phase III study involving a total of 760 male and female patients of at least 18 years of age with metastatic CRC. Patients were randomly assigned in a 2 to 1 ratio to 1 of 2 treatment groups: the experimental arm of regorafenib 160 mg once per day for 3 weeks on / 1 week off together with best supportive care (BSC) (n=505), and the comparator arm of matching placebo plus BSC (n=255).r
The primary end point was overall survival (OS) and secondary end points were progression free survival (PFS) and objective response rate (ORR).
Sub-group analyses suggest that patients with and without KRAS mutations derived similar benefits from regorafenib.
The median OS was 6.4 months in regorafenib arm vs 5.0 months in placebo group (HR=0.77; CI 95% 0.64 to 0.94; p=0.0102). The median PFS was 2.0 months in the regorafenib arm vs 1.7 months in the placebo arm (HR=0.49, CI 95% 0.42-0.58; p<0.0001). Regorafenib showed an apparent benefit in both KRAS wild type and mutated patients in PFS and OS.r
Although patient’s health related quality of life and health utility values were measured with the EORTC QLQ-C30 and EQ-5D respectively, these do not address some of the adverse events typically associated with regorafenib which were far more frequent in the regorafenib treatment arm (51% vs 12% grade 3 adverse events) and indeed most patients required dose reduction. Deterioration in patients’ quality of life and health status was not different in both regorafenib and placebo groups as measured in this study.
Progression free survivalr
© Lancet 2013
Of 110 deaths, majority were due to progression of underlying disease. 11 were attributed to adverse drug event (8 in the regorafenib group and 3 in the placebo group). 333 (67%) out of 500 patients receiving regorafenib and 57 (23%) out of 253 in the placebo group required dose adjustments due to adverse drug events, most frequent of which were dermatological, gastrointestinal, constitutional and metabolic or laboratory events.r
© Lancet 2013