P-261 Pharmacokinetics of regorafenib in the phase 3 CONCUR and CORRECT trials in patients with metastatic colorectal cancer (mCRC)

Abstract

Introduction: The CORRECT trial (NCT01103323) included 760 randomized pts in North America, Europe, Israel, Australia, and Asia (China n = 4; Japan n = 100), whereas CONCUR (NCT01584830) included a broader population of Asian pts (n = 204), mostly from China. The aim of this analysis was to compare pharmacokinetic (PK) data of REG in CONCUR and CORRECT populations. Methods: This analysis included 98 Asian pts from CONCUR and 381 pts from CORRECT. AUC(0-24),ss values for REG and its active metabolites M-2 and M-5 were calculated from sparse plasma samples determined by a previously developed population PK model for REG. Results: The range of individual AUC(0-24),ss values for REG was similar between pts in CONCUR (20.7-184 mg.h/L) and those in CORRECT (19.2-311 mg.h/L). The geometric mean AUC(0-24),ss was 64.4 mg.h/L in the 98 Asian pts from CONCUR, 69.5 mg.h/L in the 54 CONCUR pts from mainland China, and 68.1 mg.h/L in the 45 Asian pts from CORRECT, compared with 72.9 mg.h/L in the overall CORRECT population (n = 381). Ranges of AUC values for the M-2 metabolite were similar in CONCUR (2.22-233 mg.h/L) and CORRECT (3.54-295 mg.h/L) populations. Geometric mean AUC(0-24),ss values for M-2 were 42.4 mg.h/L in the 98 Asian pts from CONCUR, 47.8 mg.h/L in the 54 CONCUR pts from mainland China, 49.7 mg.h/L in the 45 Asian pts from CORRECT, and 56.7 mg.h/L in the overall CORRECT population. M-5 exposure was highly variable in both studies. Geometric mean AUC(0-24),ss values for M-5 were 33.1 mg.h/L in the 98 Asian pts from CONCUR (range 0.66- 312), 36.4 mg.h/L in the 54 CONCUR pts from mainland China (range 2.21-266), 44.9 mg.h/L in the 45 Asian pts from CORRECT (range 3.13- 315), and 54.7 mg.h/L (range 1.85-555) in the overall CORRECT population. A slightly lower mean exposure of M-5 was seen in CONCUR compared with CORRECT; however, a high intersubject variability was observed in both trials. Conclusion: REG PK (AUC(0-24),ss) for Asian mCRC patients in the CONCUR trial (including pts from Vietnam, Hong Kong, Taiwan, South Korea, and mainland China) was similar to that seen in mCRC pts in the CORRECT trial.