Masatoshi Kudo1, Etsuro Hatano2, Shinichi Ohkawa3, Hirofumi Fujii4, Akihide Masumoto5, Junji Furuse6, Yoshiyuki Wada7, Hiroshi Ishii8, Shuntaro Obi9, Shuichi Kaneko10, Seiji Kawazoe11, Osamu Yokosuka12, Masafumi Ikeda13, Katsuaki Ukai14, Sojiro Morita15, Akihito Tsuji16, Toshihiro Kudo17, Mitsuo Shimada18, Yukio Osaki19, Ryosuke Tateishi20, Gen Sugiyama21, Paolo Benjamin Abada22, Ling Yang23, Takuji Okusaka24, Andrew Xiuxuan Zhu25. 1. Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan. m-kudo@med.kinki.ac.jp. 2. Kyoto University Hospital, Kyoto, Japan. 3. Kanagawa Cancer Center, Yokohama, Kanagawa, Japan. 4. Jichi Medical University, Shimotsuke, Tochigi, Japan. 5. Aso Iizuka Hospital, Fukuoka, Japan. 6. Kyorin University School of Medicine Hospital, Tokyo, Japan. 7. National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. 8. The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan. 9. Kyoundo Hospital, Sasaki Institute, Tokyo, Japan. 10. Kanazawa University Hospital, Ishikawa, Japan. 11. Saga-Ken Medical Centre Koseikan, Saga, Japan. 12. Chiba University Hospital, Chiba, Japan. 13. National Cancer Center Hospital East, Chiba, Japan. 14. Sendai Medical Center, Sendai, Miyagi, Japan. 15. Kochi Health Sciences Center, Kochi, Japan. 16. Kagawa University Hospital, Takamatsu, Kagawa, Japan. 17. Osaka University Hospital, Osaka, Japan. 18. Tokushima University Hospital, Tokushima, Japan. 19. Osaka Red Cross Hospital, Osaka, Japan. 20. The University of Tokyo Hospital, Tokyo, Japan. 21. Kurume University Medical Center, Fukuoka, Japan. 22. Eli Lilly and Company, Indianapolis, IN, USA. 23. Eli Lilly and Company, Bridgewater, NJ, USA. 24. National Cancer Center Hospital, Tokyo, Japan. 25. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: REACH evaluated ramucirumab in the second-line treatment of patients with advanced hepatocellular carcinoma. In the intent-to-treat population (n = 565), a significant improvement in overall survival (OS) was not observed. In patients with an elevated baseline α-fetoprotein (AFP) level (400 ng/mL or greater), an improvement in OS was demonstrated. An analysis of the Japanese patients in REACH was performed. METHODS: An analysis was performed with the subset of the intent-to-treat population enrolled in Japan (n = 93). RESULTS: The median OS was 12.9 months for the ramucirumab arm (n = 45) and 8.0 months for the placebo arm (n = 48) [hazard ratio (HR) 0.621 (95 % confidence interval (CI) 0.391-0.986); P = 0.0416]. The median progression-free survival was 4.1 months for the ramucirumab arm and 1.7 months for the placebo arm [HR 0.449 (95 % CI 0.285-0.706); P = 0.0004]. The objective response rates were 11 % for the ramucirumab arm and 2 % for the placebo arm (P = 0.0817). The grade 3 or higher treatment-emergent adverse events occurring in more than 5 % of patients with a higher incidence for the ramucirumab arm (n = 44) than for the placebo arm (n = 47) were ascites (7% vs 2 %), hypertension (7 % vs 2 %), and cholangitis (7 % vs 0 %). In patients with a baseline AFP level of 400 ng/mL or greater, the median OS was 12.9 months for the ramucirumab arm (n = 20) and 4.3 months for the placebo arm (n = 22) [HR 0.464 (95 % CI 0.232-0.926); P = 0.0263]. CONCLUSIONS: In the Japanese patients in REACH, ramucirumab treatment improved OS, including in patients with a baseline AFP level of 400 ng/mL or greater; improvements in progression-free survival and objective response rate were also demonstrated. The safety profile of ramucirumab was acceptable and well tolerated in Japanese patients. ClinicalTrials.gov identifier NCT01140347.
RCT Entities:
BACKGROUND: REACH evaluated ramucirumab in the second-line treatment of patients with advanced hepatocellular carcinoma. In the intent-to-treat population (n = 565), a significant improvement in overall survival (OS) was not observed. In patients with an elevated baseline α-fetoprotein (AFP) level (400 ng/mL or greater), an improvement in OS was demonstrated. An analysis of the Japanese patients in REACH was performed. METHODS: An analysis was performed with the subset of the intent-to-treat population enrolled in Japan (n = 93). RESULTS: The median OS was 12.9 months for the ramucirumab arm (n = 45) and 8.0 months for the placebo arm (n = 48) [hazard ratio (HR) 0.621 (95 % confidence interval (CI) 0.391-0.986); P = 0.0416]. The median progression-free survival was 4.1 months for the ramucirumab arm and 1.7 months for the placebo arm [HR 0.449 (95 % CI 0.285-0.706); P = 0.0004]. The objective response rates were 11 % for the ramucirumab arm and 2 % for the placebo arm (P = 0.0817). The grade 3 or higher treatment-emergent adverse events occurring in more than 5 % of patients with a higher incidence for the ramucirumab arm (n = 44) than for the placebo arm (n = 47) were ascites (7% vs 2 %), hypertension (7 % vs 2 %), and cholangitis (7 % vs 0 %). In patients with a baseline AFP level of 400 ng/mL or greater, the median OS was 12.9 months for the ramucirumab arm (n = 20) and 4.3 months for the placebo arm (n = 22) [HR 0.464 (95 % CI 0.232-0.926); P = 0.0263]. CONCLUSIONS: In the Japanese patients in REACH, ramucirumab treatment improved OS, including in patients with a baseline AFP level of 400 ng/mL or greater; improvements in progression-free survival and objective response rate were also demonstrated. The safety profile of ramucirumab was acceptable and well tolerated in Japanese patients. ClinicalTrials.gov identifier NCT01140347.
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