Ramucirumab Confers Survival Benefit in Some Patients with Hepatocellular Carcinoma

November 2015, Vol 6, No 10

Barcelona, Spain—In the REACH trial evaluating ramucirumab (Cyramza) as second-line treatment in patients with advanced hepatocellular carcinoma after first-line therapy with sorafenib (Nexavar), overall survival (OS) was improved in the subgroup population with baseline α-fetoprotein of ?400 ng/mL (Child-Pugh class A). The OS benefits in the overall population (Child-Pugh classes A and B) did not reach significance, said lead investigator Andrew X. Zhu, MD, PhD, Massachusetts General Hospital Cancer Center, Boston.

At the 2015 European Society for Medical Oncology World Congress on Gastrointestinal Cancer, Dr Zhu said that although sorafenib is the only approved first-line treatment for patients with hepatocellular carcinoma, in the second-line setting no agent has yet demonstrated a survival benefit. Dr Zhu noted that hepatocellular carcinoma is the second most common cause of cancer death.

The REACH trial evaluated ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma after first-line therapy with sorafenib. Ramucirumab is a human immunoglobulin G1 monoclonal antibody that binds to the extracellular domain of VEGF receptor–2, preventing ligand binding and receptor activation.

Patients in the REACH trial were randomized 1:1 to intravenous ramucirumab 8 mg/kg plus best supportive care or to placebo plus best supportive care every 2 weeks until disease progression, unacceptable toxicity, or death. OS was the primary end point. When a previous analysis of results from the REACH trial showed a lack of OS improvement in the intention-to-treat population, but showed favorable findings for the subpopulation of patients with baseline α-fetoprotein of ?400 ng/mL (and Child-Pugh class A), the investigators conducted further analyses of the subpopulation’s results.

For patients with baseline α-fetoprotein of ?400 ng/mL, the OS with ramucirumab was 6.5 months compared with 4.1 months for placebo (P = .004). This benefit was derived from the patients with Child-Pugh class A, whose median OS was 7.8 months with ramucirumab versus 4.2 months with placebo (P = .005). By contrast, in patients with Child-Pugh class B, the OS was 3.7 months with ramucirumab and 2.8 months with placebo (P = .275).

Looking at the Functional Assessment of Cancer Therapy–Hepatobiliary Symptom Index-8, a tool that was designed to evaluate the symptoms of hepatobiliary cancer, Dr Zhu reported that in the population with α-fetoprotein of ?400 ng/mL, the median time to first deterioration was significantly longer with ramucirumab.

He emphasized that treatment with ramucirumab did not increase liver injury or failure, and that adverse events were generally manageable.


“REACH-2 will allow a fuller evaluation of the benefit of ramucirumab in this population with a baseline α-fetoprotein of 400 ng/mL or greater,” Dr Zhu said.

REACH-2 will include approximately 400 patients with Child-Pugh class A who will be randomized 2:1 to ramucirumab or to placebo, and both groups will receive best supportive care.

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