Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1).
BACKGROUND
S-1, an oral fluoropyrimidine, plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in East Asia. To date, no studies have evaluated the efficacy and safety of trastuzumab combined with SP in patients with human epidermal growth factor receptor type 2 (HER2)-positive AGC.


METHODS
Patients with HER2-positive AGC received S-1 (80-120 mg per day) orally on days 1-14, cisplatin (60 mg m(-2)) intravenously on day 1, and trastuzumab (course 1, 8 mg kg(-1); course 2 onward, 6 mg kg(-1)) intravenously on day 1 of a 21-day cycle. The primary end point was response rate (RR); secondary end points included overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), and adverse events.


RESULTS
A total of 56 patients were enrolled. In the full analysis set of 53 patients, the confirmed RR was 68% (95% confidence interval (CI)=54-80%), and the disease control rate was 94% (95% CI=84-99%). Median OS, PFS, and TTF were estimated as 16.0, 7.8, and 5.7 months, respectively. Major grade 3 or 4 adverse events included neutropaenia (36%), anorexia (23%), and anaemia (15%).


CONCLUSIONS
Trastuzumab in combination with SP showed promising antitumour activity and manageable toxic effects in patients with HER2-positive AGC.
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita 565-0871, Japan.
Y
Y
Kurokawa
Department of Clinical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3-1, Nakamichi, Osaka 537-8511, Japan.
N
N
Sugimoto
Department of Upper Gastroenterology, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya 663-8501, Japan.
H
H
Miwa
Department of Gastroenterological Oncology, Hyogo Cancer Center, 13-70, Kitaoji-cho, Akashi 673-8558, Japan.
M
M
Tsuda
Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2, Ohnohigashi, Osakasayama 589-8511, Japan.
S
S
Nishina
Deparment of Medical Oncology, Keiyukai Sapporo Hospital, 1-1-14, Hondori, Sapporo 003-0027, Japan.
H
H
Okuda
Deparment of Surgery, Sakai Municipal Hospital, 1-1-1, Yasui-cho, Sakai 590-0064, Japan.
H
H
Imamura
Deparment of Medical Oncology, Osaki Citizen Hospital, 2-3-10, Furukawasenjujicho, Osaki 989-6183, Japan.
M
M
Gamoh
Deparment of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Osaka 565-0871, Japan.
D
D
Sakai
Graduate School of Medicine and Engineering, University of Yamanashi, 4-4-37, Takeda, Kofu 400-8510, Japan.
T
T
Shimokawa
Deparment of Cancer Center, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
Y
Y
Komatsu
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita 565-0871, Japan.
Y
Y
Doki
Deparment of Surgery, Kaizuka City Hospital, 3-10-20, Hori, Kaizuka 597-0015, Japan.
T
T
Tsujinaka
Deparment of Surgery, Kinki University Faculty of Medicine, 377-2, Ohnohigashi, Osakasayama 589-8511, Japan.
H
H
Furukawa
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D002945:Cisplatin; D004338:Drug Combinations; D010094:Oxonic Acid; D018719:Erb-b2 Receptor Tyrosine Kinases; D005641:Tegafur; D000068878:Trastuzumab; C079198:S 1 (combination); C508053:ERBB2 protein, human