Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer.
BACKGROUND
We evaluated the safety and efficacy of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients previously treated for advanced gastric or gastroesophageal junction adenocarcinoma in Japanese and Western subgroups from the RAINBOW trial.


METHODS
Patients received ramucirumab at 8 mg/kg or placebo (days 1 and 15) plus paclitaxel at 80 mg/m(2) (days 1, 8, and 15 of a 28-day cycle). End points were compared between treatment arms within Japanese (N = 140) and Western (N = 398) populations.


RESULTS
The incidence of adverse events of grade 3 or higher was higher for ramucirumab plus paclitaxel in both populations (Japanese population, 83.8 % vs 52.1 %; Western population, 79.1 % vs 61.9 %). Neutropenia was the commonest adverse event of grade 3 or higher, with a higher incidence for ramucirumab plus paclitaxel (Japanese population, 66.2 % vs 25.4 %; Western population, 32.1 % vs 14.7 %). The incidence of febrile neutropenia was low and was similar between treatment arms in both populations. The overall survival hazard ratio was 0.88 (95 % confidence interval, 0.60-1.28) in the Japanese population and 0.73 (95 % confidence interval, 0.58-0.91) in the Western population. The progression-free survival hazard ratio was 0.50 (95 % confidence interval, 0.35-0.73) in the Japanese population and 0.63 (95 % confidence interval, 0.51-0.79) in the Western population. The objective response rate was higher for ramucirumab plus paclitaxel in both populations (Japanese population, 41.2 % vs 19.4 %; Western population, 26.8 % vs 13.0 %), as was the 6-month survival rate (Japanese population, 94.1 % vs 71.4 %; Western population, 66.0 % vs 49.0 %).


CONCLUSIONS
Safety profiles of the ramucirumab plus paclitaxel arm were similar between populations, though there was a higher incidence of neutropenia in Japanese patients. Progression-free survival and objective response rate improvements were observed for ramucirumab plus paclitaxel in both populations. CLINICALTRIALS.
NCT01170663.
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. kshitara@east.ncc.go.jp.
Kohei
K
Shitara
Aichi Cancer Center, Nagoya, Japan.
Kei
K
Muro
National Cancer Center Hospital, Tokyo, Japan.
Yasuhiro
Y
Shimada
Chiba Cancer Center, Chiba, Japan.
Shuichi
S
Hironaka
Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Naotoshi
N
Sugimoto
Hokkaido University Hospital, Sapporo, Japan.
Yoshito
Y
Komatsu
Shikoku Cancer Center, Matsuyama, Japan.
Tomohiro
T
Nishina
Saitama Cancer Center, Kita-Adachi-Gun, Japan.
Kensei
K
Yamaguchi
Saitama Medical University International Medical Center, Hidaka, Japan.
Yoshihiko
Y
Segawa
Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
Yasushi
Y
Omuro
Kinki University Faculty of Medicine, Sayama, Japan.
Takao
T
Tamura
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Toshihiko
T
Doi
Tochigi Cancer Center, Utsunomiya, Japan.
Seigo
S
Yukisawa
Shizuoka Cancer Center, Sunto-gun, Japan.
Hirofumi
H
Yasui
Kyorin University Hospital, Tokyo, Japan.
Fumio
F
Nagashima
Osaka Medical College Hospital, Takatsuki, Japan.
Masahiro
M
Gotoh
National Kyushu Cancer Center, Fukuoka, Japan.
Taito
T
Esaki
Eli Lilly and Company, Bad Homburg, Germany.
Michael
M
Emig
Eli Lilly and Company, Bridgewater, NJ, USA.
Kumari
K
Chandrawansa
Eli Lilly and Company, Indianapolis, IN, USA.
Astra M
AM
Liepa
Kliniken Essen-Mitte Center of Palliative Care, Essen, Germany.
Hansjochen
H
Wilke
Eli Lilly Japan K. K., Kobe, Japan.
Yukako
Y
Ichimiya
National Cancer Center, Tokyo, Japan.
Atsushi
A
Ohtsu
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004943:Esophagogastric Junction / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D011379:Prognosis; D011788:Quality of Life; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D044465:White People; D055815:Young Adult; D000096662:Ramucirumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000096662:Ramucirumab
Advanced gastric or gastroesophageal junction adenocarcinoma; Japanese patients; Paclitaxel; Ramucirumab; Vascular endothelial growth factor receptor 2