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Ramucirumab after prior sorafenib in patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein: Japanese subgroup analysis of the REACH-2 trial

Authors
  • Kudo, Masatoshi1
  • Okusaka, Takuji2
  • Motomura, Kenta3
  • Ohno, Izumi4
  • Morimoto, Manabu5
  • Seo, Satoru6
  • Wada, Yoshiyuki7
  • Sato, Shinpei8
  • Yamashita, Tatsuya9
  • Furukawa, Masayuki10
  • Aramaki, Takeshi11
  • Nadano, Seijin12
  • Ohkawa, Kazuyoshi13
  • Fujii, Hirofumi14
  • Kudo, Toshihiro15
  • Furuse, Junji16
  • Takai, Hiroki17
  • Homma, Gosuke17
  • Yoshikawa, Reigetsu17
  • Zhu, Andrew X.18
  • 1 Kindai University Faculty of Medicine,
  • 2 National Cancer Center Hospital,
  • 3 Aso Iizuka Hospital,
  • 4 National Cancer Center Hospital East,
  • 5 Kanagawa Cancer Center,
  • 6 Kyoto University,
  • 7 National Hospital Organization Kyushu Medical Center,
  • 8 Kyoundo Hospital, Sasaki Institute,
  • 9 Kanazawa University,
  • 10 National Hospital Organization Kyushu Cancer Center,
  • 11 Shizuoka Cancer Center Hospital,
  • 12 National Hospital Organization Shikoku Cancer Center,
  • 13 Osaka International Cancer Institute,
  • 14 Jichi Medical University,
  • 15 Osaka University,
  • 16 Kyorin University Faculty of Medicine,
  • 17 Eli Lilly Japan K.K.,
  • 18 Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA USA
Type
Published Article
Journal
Journal of Gastroenterology
Publisher
Springer Singapore
Publication Date
Feb 27, 2020
Volume
55
Issue
6
Pages
627–639
Identifiers
DOI: 10.1007/s00535-020-01668-w
PMID: 32107609
PMCID: PMC7242235
Source
PubMed Central
Keywords
License
Unknown

Abstract

Background The global, randomized, phase 3 REACH-2 study (ClinicalTrials.gov identifier: NCT02435433) found significantly longer overall survival (OS) for second-line ramucirumab versus placebo (hazard ratio [HR]: 0.710, 95% confidence interval [CI] 0.531–0.949, P = 0.0199) in patients with advanced hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) ≥ 400 ng/mL. This prespecified subgroup analysis evaluated the efficacy and safety of ramucirumab in the Japanese patients enrolled in the study. Methods Patients with advanced HCC and AFP ≥ 400 ng/mL after first-line sorafenib were randomized 2:1 to ramucirumab (8 mg/kg intravenously) or placebo every 2 weeks. Hazard ratios for progression-free survival (PFS) and OS (primary endpoint of the overall study) were estimated using the stratified Cox regression model. We also pooled individual patient data from REACH-2 with data from REACH (NCT01140347) for patients with AFP ≥ 400 ng/mL. Results In the Japanese REACH-2 subpopulation, there were improvements for ramucirumab ( n = 41) versus placebo ( n = 18) in PFS (HR 0.282, 95% CI 0.144–0.553) and OS was numerically prolonged (HR 0.599, 95% CI 0.303–1.187), consistent with the significant benefit seen in the overall REACH-2 study population. In the ramucirumab and placebo arms, respectively, the objective response rate was 7.3% and 0%, and the disease control rate was 70.7% and 33.3%. The most frequently reported grade ≥ 3 treatment-emergent adverse event was hypertension (ramucirumab: 15%; placebo: 11%). Conclusions Ramucirumab after prior sorafenib improved PFS and OS compared with placebo, with a manageable safety profile, in the Japanese REACH-2 subpopulation, consistent with the overall REACH-2 study results. Ramucirumab is the first agent to demonstrate clinical benefit for Japanese patients with HCC in the second-line setting. Electronic supplementary material The online version of this article (10.1007/s00535-020-01668-w) contains supplementary material, which is available to authorized users.

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