caa a22 4500 605491526 CHVBK 20210128100510.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s10147-015-0790-y doi (NATIONALLICENCE)springer-10.1007/s10147-015-0790-y Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial [Elektronische Daten] [Yoshito Komatsu, Toshihiko Doi, Akira Sawaki, Tatsuo Kanda, Yasuhide Yamada, Iris Kuss, George Demetri, Toshirou Nishida] 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 160mg 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. Japan Society of Clinical Oncology, 2015 Regorafenib nationallicence Japanese nationallicence Gastrointestinal stromal tumor nationallicence Hand-foot syndrome nationallicence Hypertension nationallicence Komatsu Yoshito Cancer Center, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, 060-8648, Sapporo, Hokkaido, Japan aut Doi Toshihiko National Cancer Center Hospital East, Kashiwa, Japan aut Sawaki Akira Department of Oncology and Gastroenterology, Nagoya Second Red Cross Hospital, Nagoya, Japan aut Kanda Tatsuo Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan aut Yamada Yasuhide Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan aut Kuss Iris Global Clinical Development, Oncology, Ophthalmology and Neurology, Bayer Pharma AG, Berlin, Germany aut Demetri George Ludwig Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA aut Nishida Toshirou Department of Surgery, National Cancer Center Hospital East, Kashiwa, Japan aut International Journal of Clinical Oncology Springer Japan 20/5(2015-10-01), 905-912 1341-9625 20:5<905 2015 20 10147 https://doi.org/10.1007/s10147-015-0790-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10147-015-0790-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Komatsu Yoshito Cancer Center, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, 060-8648, Sapporo, Hokkaido, Japan aut NATIONALLICENCE 700 1- Doi Toshihiko National Cancer Center Hospital East, Kashiwa, Japan aut NATIONALLICENCE 700 1- Sawaki Akira Department of Oncology and Gastroenterology, Nagoya Second Red Cross Hospital, Nagoya, Japan aut NATIONALLICENCE 700 1- Kanda Tatsuo Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan aut NATIONALLICENCE 700 1- Yamada Yasuhide Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan aut NATIONALLICENCE 700 1- Kuss Iris Global Clinical Development, Oncology, Ophthalmology and Neurology, Bayer Pharma AG, Berlin, Germany aut NATIONALLICENCE 700 1- Demetri George Ludwig Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA aut NATIONALLICENCE 700 1- Nishida Toshirou Department of Surgery, National Cancer Center Hospital East, Kashiwa, Japan aut NATIONALLICENCE 773 0- International Journal of Clinical Oncology Springer Japan 20/5(2015-10-01), 905-912 1341-9625 20:5<905 2015 20 10147