Randomized phase III trial of regorafenib in metastatic colorectal cancer: analysis of the CORRECT Japanese and non-Japanese subpopulations

Takayuki Yoshino, Yoshito Komatsu, Yasuhide Yamada, Kentaro Yamazaki, Akihito Tsuji, Takashi Ura, Axel Grothey, Eric Van Cutsem, Andrea Wagner, Frank Cihon, Yoko Hamada, Atsushi Ohtsu, Takayuki Yoshino, Yoshito Komatsu, Yasuhide Yamada, Kentaro Yamazaki, Akihito Tsuji, Takashi Ura, Axel Grothey, Eric Van Cutsem, Andrea Wagner, Frank Cihon, Yoko Hamada, Atsushi Ohtsu

Abstract

Background: In the international, phase III, randomized, double-blind CORRECT trial, regorafenib significantly prolonged overall survival (OS) versus placebo in patients with metastatic colorectal cancer (mCRC) that had progressed on all standard therapies. This post hoc analysis evaluated the efficacy and safety of regorafenib in Japanese and non-Japanese subpopulations in the CORRECT trial.

Methods: Patients were randomized 2 : 1 to regorafenib 160 mg once daily or placebo for weeks 1-3 of each 4-week cycle. The primary endpoint was OS. Outcomes were assessed using descriptive statistics.

Results: One hundred Japanese and 660 non-Japanese patients were randomized to regorafenib (n = 67 and n = 438) or placebo (n = 33 and n = 222). Regorafenib had a consistent OS benefit in the Japanese and non-Japanese subpopulations, with hazard ratios of 0.81 (95 % confidence interval [CI] 0.43-1.51) and 0.77 (95 % CI 0.62-0.94), respectively. Regorafenib-associated hand-foot skin reaction, hypertension, proteinuria, thrombocytopenia, and lipase elevations occurred more frequently in the Japanese subpopulation than in the non-Japanese subpopulation, but were generally manageable.

Conclusion: Regorafenib appears to have comparable efficacy in Japanese and non-Japanese subpopulations, with a manageable adverse-event profile, suggesting that this agent could potentially become a standard of care in patients with mCRC.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curves showing overall survival and progression-free survival in Japanese (a and b, respectively) and non-Japanese patients (c and d, respectively)
Fig. 2
Fig. 2
Maximum percentage change in target lesion size in (a) Japanese patients and (b) non-Japanese patients
Fig. 3
Fig. 3
Distribution of area under the concentration–time curve over a 24-h dosing interval (AUC0–24) of (a) regorafenib, (b) M2 and (c) M5 in Japanese and non-Japanese patients. Boxes represent the median and interquartile range of AUC0–24 of regorafenib, M2 and M5; whiskers represent the range between the lowest and highest values within 1.5 times the first and third quartiles. Dots represent outlying values greater than 1.5 times the third quartile

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