Analysis of the REACH study provides new strategy to predict patients most likely to benefit from liver cancer treatment

California Pacific CURRENTS: The online journal of CPMC Research Institute

January 19, 2016

Few options are available to treat patients with advanced hepatocellular carcinoma (HCC)—a severe type of liver cancer. Investigators at California Pacific Medical Center (CPMC)’s Liver Cancer Program are developing new treatment approaches that will advance patient care.

In 2015, Ari Baron, MD, Medical Director of the Clinical Oncology Research Program at CPMC, Chief of the Division of Hematology-Oncology and CPMC Research Institute investigator co-authored the REACH phase 3 study, which studied the efficacy and safety of the monoclonal antibody ramucirumab for the treatment of HCC.

In the multicenter, randomized, placebo-controlled, double-blind trial, 565 patients who had received prior therapy with sorafenib (the only FDA-approved treatment for liver cancer) were given ramucirumab or placebo every two weeks from November 2010 to April 2013. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival, time to progression, and safety.

Results suggested that ramucirumab had anti-tumor activity in some patients with advanced disease, but that a method to pre-select patients most likely to derive a survival benefit was required.

An analysis of the REACH trial results by Child-Pugh Score was published in September, 2016 in JAMA Oncology.   

In the study, Dr. Baron and colleagues at Massachusetts General Hospital Cancer Center and Harvard Medical School explored outcomes of ramucirumab in the context of the severity of underlying liver disease (i.e., Child-Pugh score).

Overall, 643 patients were randomized and included in the REACH analysis: 565 patients were considered Child-Pugh class A (Child-Pugh scores 5 and 6) and 78 patients were considered class B (Child-Pugh scores 7 and 8). The primary outcome of the study was OS, defined as time from randomization to death from any cause.

Results showed that in patients with healthier livers (a score of 5), there was a strong trend in support of the drug for all patients (p= 0.06).  In patients with elevated levels of alpha-fetoprotein (AFP)—a commonly used blood test to assess the disease—there was survival benefit for all patients with a Child-Pugh score of 5 or 6.

“Ramucirumab is a vascular endothelial growth factor (VEGF) receptor blocker, meaning it inhibits the proteins that promote blood vessel growth in tumors. As a second-line treatment for liver cancer, the drug showed a strong trend for survival for all patients with better underlying liver function, and a clear survival advantage for the same patients with an elevated AFP marker,” said Dr. Baron.

“Our analysis further refines the outcome in the context of underlying liver disease.”

The study was supported by Eli Lilly and Company.

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