Kohei Shitara1, Kei Muro2, Yasuhiro Shimada3, Shuichi Hironaka4, Naotoshi Sugimoto5, Yoshito Komatsu6, Tomohiro Nishina7, Kensei Yamaguchi8, Yoshihiko Segawa9, Yasushi Omuro10, Takao Tamura11, Toshihiko Doi12, Seigo Yukisawa13, Hirofumi Yasui14, Fumio Nagashima15, Masahiro Gotoh16, Taito Esaki17, Michael Emig18, Kumari Chandrawansa19, Astra M Liepa20, Hansjochen Wilke21, Yukako Ichimiya22, Atsushi Ohtsu23. 1. 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. 2. Aichi Cancer Center, Nagoya, Japan. 3. National Cancer Center Hospital, Tokyo, Japan. 4. Chiba Cancer Center, Chiba, Japan. 5. Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. 6. Hokkaido University Hospital, Sapporo, Japan. 7. Shikoku Cancer Center, Matsuyama, Japan. 8. Saitama Cancer Center, Kita-Adachi-Gun, Japan. 9. Saitama Medical University International Medical Center, Hidaka, Japan. 10. Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. 11. Kinki University Faculty of Medicine, Sayama, Japan. 12. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 13. Tochigi Cancer Center, Utsunomiya, Japan. 14. Shizuoka Cancer Center, Sunto-gun, Japan. 15. Kyorin University Hospital, Tokyo, Japan. 16. Osaka Medical College Hospital, Takatsuki, Japan. 17. National Kyushu Cancer Center, Fukuoka, Japan. 18. Eli Lilly and Company, Bad Homburg, Germany. 19. Eli Lilly and Company, Bridgewater, NJ, USA. 20. Eli Lilly and Company, Indianapolis, IN, USA. 21. Kliniken Essen-Mitte Center of Palliative Care, Essen, Germany. 22. Eli Lilly Japan K. K., Kobe, Japan. 23. National Cancer Center, Tokyo, Japan.
Abstract
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. GOV IDENTIFIER: NCT01170663.
RCT Entities:
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. GOV IDENTIFIER: NCT01170663.
Entities:
Keywords:
Advanced gastric or gastroesophageal junction adenocarcinoma; Japanese patients; Paclitaxel; Ramucirumab; Vascular endothelial growth factor receptor 2
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