Journal of Gastroenterology

, Volume 52, Issue 4, pp 494–503

Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial

  • Masatoshi Kudo
  • Etsuro Hatano
  • Shinichi Ohkawa
  • Hirofumi Fujii
  • Akihide Masumoto
  • Junji Furuse
  • Yoshiyuki Wada
  • Hiroshi Ishii
  • Shuntaro Obi
  • Shuichi Kaneko
  • Seiji Kawazoe
  • Osamu Yokosuka
  • Masafumi Ikeda
  • Katsuaki Ukai
  • Sojiro Morita
  • Akihito Tsuji
  • Toshihiro Kudo
  • Mitsuo Shimada
  • Yukio Osaki
  • Ryosuke Tateishi
  • Gen Sugiyama
  • Paolo Benjamin Abada
  • Ling Yang
  • Takuji Okusaka
  • Andrew Xiuxuan Zhu
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-016-1247-4

Cite this article as:
Kudo, M., Hatano, E., Ohkawa, S. et al. J Gastroenterol (2017) 52: 494. doi:10.1007/s00535-016-1247-4

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.

Keywords

α-Fetoprotein Clinical trial Japan Liver neoplasms Vascular endothelial growth factor receptor 2 

Supplementary material

535_2016_1247_MOESM1_ESM.docx (45 kb)
Supplementary material 1 (DOCX 44 kb)
535_2016_1247_MOESM2_ESM.docx (47 kb)
Supplementary material 2 (DOCX 46 kb)
535_2016_1247_MOESM3_ESM.docx (47 kb)
Supplementary material 3 (DOCX 47 kb)

Copyright information

© Japanese Society of Gastroenterology 2016

Authors and Affiliations

  • Masatoshi Kudo
    • 1
  • Etsuro Hatano
    • 2
  • Shinichi Ohkawa
    • 3
  • Hirofumi Fujii
    • 4
  • Akihide Masumoto
    • 5
  • Junji Furuse
    • 6
  • Yoshiyuki Wada
    • 7
  • Hiroshi Ishii
    • 8
  • Shuntaro Obi
    • 9
  • Shuichi Kaneko
    • 10
  • Seiji Kawazoe
    • 11
  • Osamu Yokosuka
    • 12
  • Masafumi Ikeda
    • 13
  • Katsuaki Ukai
    • 14
  • Sojiro Morita
    • 15
  • Akihito Tsuji
    • 16
  • Toshihiro Kudo
    • 17
  • Mitsuo Shimada
    • 18
  • Yukio Osaki
    • 19
  • Ryosuke Tateishi
    • 20
  • Gen Sugiyama
    • 21
  • Paolo Benjamin Abada
    • 22
  • Ling Yang
    • 23
  • Takuji Okusaka
    • 24
  • Andrew Xiuxuan Zhu
    • 25
  1. 1.Kindai University Faculty of MedicineOsaka-SayamaJapan
  2. 2.Kyoto University HospitalKyotoJapan
  3. 3.Kanagawa Cancer CenterYokohamaJapan
  4. 4.Jichi Medical UniversityShimotsukeJapan
  5. 5.Aso Iizuka HospitalFukuokaJapan
  6. 6.Kyorin University School of Medicine HospitalTokyoJapan
  7. 7.National Hospital Organization Kyushu Medical CenterFukuokaJapan
  8. 8.The Cancer Institute Hospital of the Japanese Foundation for Cancer ResearchTokyoJapan
  9. 9.Kyoundo HospitalSasaki InstituteTokyoJapan
  10. 10.Kanazawa University HospitalIshikawaJapan
  11. 11.Saga-Ken Medical Centre KoseikanSagaJapan
  12. 12.Chiba University HospitalChibaJapan
  13. 13.National Cancer Center Hospital EastChibaJapan
  14. 14.Sendai Medical CenterSendaiJapan
  15. 15.Kochi Health Sciences CenterKochiJapan
  16. 16.Kagawa University HospitalTakamatsuJapan
  17. 17.Osaka University HospitalOsakaJapan
  18. 18.Tokushima University HospitalTokushimaJapan
  19. 19.Osaka Red Cross HospitalOsakaJapan
  20. 20.The University of Tokyo HospitalTokyoJapan
  21. 21.Kurume University Medical CenterFukuokaJapan
  22. 22.Eli Lilly and CompanyIndianapolisUSA
  23. 23.Eli Lilly and CompanyBridgewaterUSA
  24. 24.National Cancer Center HospitalTokyoJapan
  25. 25.Massachusetts General Hospital Cancer CenterHarvard Medical SchoolBostonUSA