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 F Grothey, Eric Van Cutsem, Andrea Wagner, Frank Cihon, Yoko Hamada, Atsushi Ohtsu

Research output: Contribution to journalArticle

52 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)740-750
Number of pages11
JournalInvestigational New Drugs
Volume33
Issue number3
DOIs
StatePublished - Jun 22 2015

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Colorectal Neoplasms
Placebos
Survival
Confidence Intervals
Standard of Care
regorafenib
Lipase
Proteinuria
Thrombocytopenia
Foot
Hand
Hypertension
Safety
Skin

Keywords

  • Clinical trial
  • Colorectal cancer
  • Japanese
  • Phase III
  • Protein kinase inhibitors
  • Regorafenib

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

Randomized phase III trial of regorafenib in metastatic colorectal cancer : Analysis of the CORRECT Japanese and non-Japanese subpopulations. / Yoshino, Takayuki; Komatsu, Yoshito; Yamada, Yasuhide; Yamazaki, Kentaro; Tsuji, Akihito; Ura, Takashi; Grothey, Axel F; Van Cutsem, Eric; Wagner, Andrea; Cihon, Frank; Hamada, Yoko; Ohtsu, Atsushi.

In: Investigational New Drugs, Vol. 33, No. 3, 22.06.2015, p. 740-750.

Research output: Contribution to journalArticle

Yoshino, T, Komatsu, Y, Yamada, Y, Yamazaki, K, Tsuji, A, Ura, T, Grothey, AF, Van Cutsem, E, Wagner, A, Cihon, F, Hamada, Y & Ohtsu, A 2015, 'Randomized phase III trial of regorafenib in metastatic colorectal cancer: Analysis of the CORRECT Japanese and non-Japanese subpopulations', Investigational New Drugs, vol. 33, no. 3, pp. 740-750. https://doi.org/10.1007/s10637-014-0154-x
Yoshino, Takayuki ; Komatsu, Yoshito ; Yamada, Yasuhide ; Yamazaki, Kentaro ; Tsuji, Akihito ; Ura, Takashi ; Grothey, Axel F ; Van Cutsem, Eric ; Wagner, Andrea ; Cihon, Frank ; Hamada, Yoko ; Ohtsu, Atsushi. / Randomized phase III trial of regorafenib in metastatic colorectal cancer : Analysis of the CORRECT Japanese and non-Japanese subpopulations. In: Investigational New Drugs. 2015 ; Vol. 33, No. 3. pp. 740-750.
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AU - Yoshino, Takayuki

AU - Komatsu, Yoshito

AU - Yamada, Yasuhide

AU - Yamazaki, Kentaro

AU - Tsuji, Akihito

AU - Ura, Takashi

AU - Grothey, Axel F

AU - Van Cutsem, Eric

AU - Wagner, Andrea

AU - Cihon, Frank

AU - Hamada, Yoko

AU - Ohtsu, Atsushi

PY - 2015/6/22

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N2 - 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.

AB - 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.

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