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Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial

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Abstract

Background

The randomized, double-blind, placebo-controlled GRID trial tested the oral multikinase inhibitor regorafenib in 199 patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib, and showed a significant improvement in progression-free survival (PFS) versus placebo [hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.19–0.39; p < 0.0001].

Methods

A subgroup analysis of Japanese patients in the GRID study was performed to compare the efficacy and safety of oral regorafenib 160 mg once daily with matching placebo, in combination with best supportive care. The primary study endpoint was progression-free survival (PFS); safety was evaluated through the incidence of adverse events (AEs).

Results

Seventeen Japanese patients were randomized to regorafenib (n = 12) or placebo (n = 5). Patient demographics were consistent with those of the overall study population. PFS was significantly longer with regorafenib than placebo (HR 0.08; 95 % CI 0.02–0.45; p = 0.000164). Centrally assessed disease control rates were 58 % and 20 % in the regorafenib and placebo groups, respectively (p = 0.080796). Treatment-related adverse events (AEs) were reported in all regorafenib-treated patients and 60 % of placebo recipients; the most frequent AE was hand–foot skin reaction (HFSR) (92 % versus 20 %, respectively).

Conclusion

Regorafenib showed efficacy and a manageable safety profile in Japanese patients with advanced GIST, consistent with the overall GRID study population. AEs, such as HFSR and maculopapular rash, were observed more frequently in Japanese patients. Although dose modification was frequently reported, only one patient with hepatic failure discontinued regorafenib because of AEs.

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Acknowledgments

We thank the participating patients and staff at each of the study centers. Editorial assistance in the preparation of this manuscript was provided by Succinct Medical Communications, with financial support from Bayer Health Care Pharmaceuticals; the authors retained editorial control over the content.

Conflict of interest

Yoshito Komatsu has received honoraria and research funding from Bayer. Yasuhide Yamada has received honoraria from Taiho, Chugai, and Pfizer and research funding from Novartis, Astrazeneca, Otsuka, MerckSerono, Chugai, and Daiichi-Sankyo. Iris Kuss owns stocks in Bayer. George Demetri has acted as a consultant to Kolltan Pharmaceuticals, Blueprint Medicines, G1 Therapeutics, Caris, Champions Oncology, and Bessor Pharmaceuticals (uncompensated), Pfizer, EMD-Serono, Sanofi Oncology, Janssen Oncology, Glaxo-Smith-Kline, Ariad, Astra-Zeneca, WIRB Copernicus Group, and Bayer. He has received research support from Bayer, Novartis, Pfizer, EMD-Serono, Sanofi Oncology, Janssen Oncology and Glaxo-Smith-Kline. He has equity in Kolltan Pharmaceuticals, Blueprint Medicines, G1 Therapeutics, Caris, Champions Oncology, and Bessor Pharmaceuticals. He has been part of scientific advisory boards for Kolltan Pharmaceuticals, Blueprint Medicines, G1 Therapeutics, Caris, and Champions Oncology and has provided noncompensated expert regulatory testimony on behalf of Bayer and Glaxo-Smith-Kline. Toshirou Nishida has received honoraria from Novartis, Pfizer, and Bayer and a research grant from Novartis. Toshihiko Doi, Akira Sawaki, and Tatsuo Kanda have no relevant conflicts of interest to declare.

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Authors and Affiliations

  1. Cancer Center, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan

    Yoshito Komatsu

  2. National Cancer Center Hospital East, Kashiwa, Japan

    Toshihiko Doi

  3. Department of Oncology and Gastroenterology, Nagoya Second Red Cross Hospital, Nagoya, Japan

    Akira Sawaki

  4. Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Tatsuo Kanda

  5. Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan

    Yasuhide Yamada

  6. Global Clinical Development, Oncology, Ophthalmology and Neurology, Bayer Pharma AG, Berlin, Germany

    Iris Kuss

  7. Ludwig Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    George D. Demetri

  8. Department of Surgery, National Cancer Center Hospital East, Kashiwa, Japan

    Toshirou Nishida

Authors
  1. Yoshito Komatsu
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  2. Toshihiko Doi
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  3. Akira Sawaki
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  4. Tatsuo Kanda
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  5. Yasuhide Yamada
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  6. Iris Kuss
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  7. George D. Demetri
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  8. Toshirou Nishida
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Corresponding author

Correspondence to Yoshito Komatsu.

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Komatsu, Y., Doi, T., Sawaki, A. et al. Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial. Int J Clin Oncol 20, 905–912 (2015). https://doi.org/10.1007/s10147-015-0790-y

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  • DOI: https://doi.org/10.1007/s10147-015-0790-y

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