TY - JOUR
T1 - Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2-positive gastric cancer
T2 - a phase II trial and biomarker study (WJOG7212G)
AU - Miura, Yuji
AU - Sukawa, Yasutaka
AU - Hironaka, Shuichi
AU - Mori, Misuzu
AU - Nishikawa, Kazuhiro
AU - Tokunaga, Shinya
AU - Okuda, Hiroyuki
AU - Sakamoto, Takeshi
AU - Taku, Keisei
AU - Nishikawa, Kazuo
AU - Moriwaki, Toshikazu
AU - Negoro, Yuji
AU - Kimura, Yutaka
AU - Uchino, Keita
AU - Shinozaki, Katsunori
AU - Shinozaki, Hiroharu
AU - Musha, Nobuyuki
AU - Yoshiyama, Hirotsugu
AU - Tsuda, Takashi
AU - Miyata, Yoshinori
AU - Sugimoto, Naotoshi
AU - Shirakawa, Tsuyoshi
AU - Ito, Miki
AU - Yonesaka, Kimio
AU - Yoshimura, Kenichi
AU - Boku, Narikazu
AU - Nosho, Katsuhiko
AU - Takano, Toshimi
AU - Hyodo, Ichinosuke
N1 - Funding Information:
This trial was funded by a research contract from Taiho Pharmaceutical Co. Ltd, Japan. The translational aspect of the trial was also supported by the Japan Society for the Promotion of Science (KAKENHI 26430174). Yuji Miura received honoraria from Novartis and Kyowa Hakko Kirin. Ichinosuke Hyodo received honoraria from Taiho, Chugai, Daiichi-Sankyo, Yakult-Honsha, and Eli Lilly. Toshikazu Moriwaki received honoraria from Taiho, Chugai, and Takeda and research funding from Taiho, Sanofi, Boehringer Ingelheim, and MSD. Kazuhiro Nishikawa received honoraria from Taiho, Chugai, Yakult, and Ajinomoto. Naotoshi Sugimoto received research funding from Taiho, Daiichi-Sankyo, and Eli Lilly. Kenichi Yoshimura received honoraria from Taiho and Chugai. The remaining authors declare that they have no conflict of interest.
Funding Information:
Acknowledgements This trial was funded by a research contract from Taiho Pharmaceutical Co. Ltd, Japan. The translational aspect of the trial was also supported by the Japan Society for the Promotion of Science (KAKENHI 26430174).
Publisher Copyright:
© 2017, The International Gastric Cancer Association and The Japanese Gastric Cancer Association.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background: Five-weekly S-1 plus cisplatin (SP) therapy is the standard care for advanced gastric or esophagogastric junction cancer (GC/EGJC) in East Asia. However, its efficacy and safety when combined with trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced GC/EGJC remains unclear. Methods: Patients received 5-weekly SP therapy (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/m2 on day 8, every 5 weeks) plus trastuzumab therapy (first dose of 8 mg/kg, then 6 mg/kg every 3 weeks). The primary end point was the response rate, and the secondary end points included progression-free survival, overall survival, safety, and serum biomarker levels. Results: Forty-four patients were enrolled. The response rate, progression-free survival, and overall survival were 61% (95% confidence interval 46–76%), 5.9 months, and 16.5 months respectively. The commonest grade 3 or grade 4 adverse events were neutropenia (30%) and anorexia (25%). A significantly higher response rate (92% vs 43%; P = 0.008) and longer progression-free survival (median 14.5 months vs 4.2 months; P = 0.028) were observed in patients with high (n = 14) compared with low (n = 17) pretreatment serum neuregulin 1 levels. Conclusions: Five-weekly SP therapy combined with trastuzumab therapy showed a good antitumor response and acceptable toxicity in HER2-positive advanced GC/EGJC. Serum neuregulin 1 might be associated with the efficacy of this treatment regimen.
AB - Background: Five-weekly S-1 plus cisplatin (SP) therapy is the standard care for advanced gastric or esophagogastric junction cancer (GC/EGJC) in East Asia. However, its efficacy and safety when combined with trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced GC/EGJC remains unclear. Methods: Patients received 5-weekly SP therapy (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/m2 on day 8, every 5 weeks) plus trastuzumab therapy (first dose of 8 mg/kg, then 6 mg/kg every 3 weeks). The primary end point was the response rate, and the secondary end points included progression-free survival, overall survival, safety, and serum biomarker levels. Results: Forty-four patients were enrolled. The response rate, progression-free survival, and overall survival were 61% (95% confidence interval 46–76%), 5.9 months, and 16.5 months respectively. The commonest grade 3 or grade 4 adverse events were neutropenia (30%) and anorexia (25%). A significantly higher response rate (92% vs 43%; P = 0.008) and longer progression-free survival (median 14.5 months vs 4.2 months; P = 0.028) were observed in patients with high (n = 14) compared with low (n = 17) pretreatment serum neuregulin 1 levels. Conclusions: Five-weekly SP therapy combined with trastuzumab therapy showed a good antitumor response and acceptable toxicity in HER2-positive advanced GC/EGJC. Serum neuregulin 1 might be associated with the efficacy of this treatment regimen.
KW - First-line chemotherapy
KW - Gastric adenocarcinoma
KW - Neuregulin 1
KW - S-1
KW - Trastuzumab
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U2 - 10.1007/s10120-017-0725-6
DO - 10.1007/s10120-017-0725-6
M3 - Article
AN - SCOPUS:85019083751
SN - 1436-3291
VL - 21
SP - 84
EP - 95
JO - Gastric Cancer
JF - Gastric Cancer
IS - 1
ER -
