Identify Subset of Patients Benefiting from Treatment for Patients with Liver Cancer

• Activity Number: 639
• Type: Topic Contributed
• Date/Time: Thursday, August 13, 2015 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Yihuan Xu* and Yanzhi Hsu and Ling Yang
• Companies: Eli Lilly and Company and Eli Lilly and Company and Eli Lilly and Company
• Keywords: optimal cutoff value ; subgroup analysis ; Cox regression ; alpha-fetoprotein (AFP)

Abstract

REACH was a phase 3 randomized double-blind global study of ramucirumab in advanced hepatocellular carcinoma (HCC) after prior sorafenib therapy. Serum alpha-fetoprotein (AFP) is a common prognostic lab test for patients with HCC. AFP level is a continuous measurement with normal value generally below 10 ng/mL, but the range is extremely wide in HCC patients. In REACH, a pre-specified subgroup analysis suggested that patients with baseline AFP >= 400 ng/mL had a survival benefit from ramucirumab treatment. Additional analyses using Cox regression models with AFP as continuous variable confirmed the statistically significant interaction between AFP levels and treatment. Therefore it is desirable to determine an optimal cutoff of AFP to identify a subset of patients who are more likely to benefit from the treatment. A wide range of AFP cutoff values were explored, and the analyses demonstrated a consistent ramucirumab survival benefit for the patient subpopulations with baseline AFP over a wide range of values above the normal range.