Ramucirumab in advanced hepatocellular carcinoma in REACH-2: the true value of α-fetoprotein

• Published in: The lancet oncology 2019-04, Vol.20 (4), p.e191-e191
• Main Authors: Zhu, Andrew X, Finn, Richard S, Galle, Peter R, Llovet, Josep M, Kudo, Masatoshi
• Format: Article
• Language: English
• Subjects: alpha-Fetoproteins; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biomarkers; Carcinoma, Hepatocellular; Chief executive officers; Clinical trials; Fees & charges; Hepatocellular carcinoma; Humans; Liver cancer; Liver Neoplasms; Medical prognosis; Ramucirumab
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(19)30165-2

[...]by contrast with the claim that the prognostic value of α-fetoprotein “has been shown only in a few retrospective studies”, its association with poor prognosis at high concentrations has been consistently shown in several phase 3 clinical studies, including SHARP (NCT00105443), REFLECT (NCT01761266), RESORCE,4 CELESTIAL (NCT01908426), REACH (NCT01140347), and a large Japanese nationwide prospective registry of 173 378 patients.5 In fact, high baseline α-fetoprotein concentration has been increasingly used as a stratification factor in phase 3 clinical trial design in advanced hepatocellular carcinoma.4 Third, many efforts to use a biomarker selection strategy have failed in clinical trial design in advanced hepatocellular carcinoma, including in the recent phase 3 trial with tivantinib in second-line treatment of high MET expression hepatocellular carcinoma.6 Therefore, REACH-2 represents the first positive phase 3 trial in a biomarker-selected population with hepatocellular carcinoma. [...]α-fetoprotein is a biomarker with proven prognostic and predictive value in hepatocellular carcinoma. AXZ reports grants from Bayer, Bristol-Myers Squibb, Eli Lilly, Merck, and Novartis, and consultancy fees and advisory roles for AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Eli Lilly, Exelixis, Merck, Novartis, and Roche Genentech.