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

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Pharmacology
Colon Cancer
Rectal Cancer
Presenter A. Cleton
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors A. Cleton1, I. Sturm1, Z. Jirakova Trnkova1, J. Grevel2, S. Fiala-Buskies3, J. Lettieri4
  • 1Bayer Pharma AG, Berlin/DE
  • 2BAST Inc. Limited, Loughborough/UK
  • 3Bayer Pharma AG, Wuppertal/DE
  • 4Bayer Healthcare, Whippany/US

Abstract

Introduction

Two randomized, double-blind, placebo-controlled multi-center phase 3 trials have shown that regorafenib (160 mg, 3 weeks on/1 week off) improves overall survival in patients with treatment-refractory mCRC. The CORRECT trial (NCT01103323) included 760 randomized patients in North America, Europe, Israel, Australia, and Asia (China n = 4; Japan n = 100), whereas CONCUR (NCT01584830) included a broader population of Asian patients (n = 204), mostly from China. The aim of this analysis was to compare pharmacokinetic (PK) data of regorafenib in the CONCUR and CORRECT patient populations.

Methods

This analysis included 98 Asian patients from CONCUR (mainland China, n = 54; South Korea, n = 14; Taiwan, n = 13; Hong Kong, n = 8; and Vietnam, n = 9) and 381 patients from CORRECT (White, n = 310; Asian, n = 45; other, n = 26). Of the 45 Asian patients in CORRECT, 41 were from Japan. The AUC(0–24),ss values for regorafenib and its active metabolites M-2 and M-5 were calculated from sparse plasma samples (up to 2–5 samples per patient in CORRECT, up to 4 samples per patient in CONCUR) determined by a previously developed population PK model for regorafenib.

Results

The range of individual AUC(0–24),ss values for regorafenib was similar between patients 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 patients from CONCUR, 69.5 mg·h/L in the 54 CONCUR patients from mainland China, and 68.1 mg·h/L in the 45 Asian patients from CORRECT, compared with 72.9 mg·h/L in the overall CORRECT patient 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) patient populations. Geometric mean AUC(0–24),ss values for M-2 were 42.4 mg·h/L in the 98 Asian patients from CONCUR, 47.8 mg·h/L in the 54 CONCUR patients from mainland China, 49.7 mg·h/L in the 45 Asian patients 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 patients from CONCUR (range 0.66–312), 36.4 mg·h/L in the 54 CONCUR patients from mainland China (range 2.21–266), 44.9 mg·h/L in the 45 Asian patients 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

The regorafenib PK (AUC(0–24),ss) for Asian mCRC patients in the CONCUR trial (including patients from Vietnam, Hong Kong, Taiwan, South Korea, and mainland China) was similar to that seen in mCRC patients in the CORRECT trial.