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Cyramza does not significantly improve OS in patients with advanced HCC

Phase 3 results from the REACH study showed that Cyramza therapy did not significantly improve survival more than placebo in patients with advanced hepatocellular carcinoma after treatment with sorafenib, according to new data published in The Lancet Oncology.

“Advanced liver cancer carries a poor prognosis with limited treatment options,” Andrew X. Zhu, MD, director of Liver Cancer Research at Massachusetts General Hospital Cancer Center and investigator of the REACH trial, said in a press release. “Several phase 3 studies to date have not been able to demonstrate improved survival in the second-line setting following sorafenib failure. Further analyses from the REACH study have identified [alpha-fetoprotein] as a potential marker for selecting patients with advanced hepatocellular carcinoma who may benefit from ramucirumab treatment.”

Zhu and colleagues recruited 565 patients with advanced HCC who completed first-line treatment with Nexavar (sorafenib, Bayer) from 154 centers in 27 countries between November 2010 and April 2013. They were randomly assigned to receive 8 mg/kg of Cyramza (ramucirumab, Eli Lilly; n = 283) or placebo (n = 282) every 2 weeks, plus supportive care. Patients were followed until disease progression, unacceptable toxicity or mortality. The median duration of therapy for patients who received ramucirumab was 12 weeks vs. 8 weeks in patients who received placebo.

The median overall survival for patients treated with ramucirumab was 9.2 months and 7.6 months for patients treated with placebo (HR = 0.87; 95% CI, 0.72-1.05). The median to progression-free survival was 2.8 months for ramucirumab patients vs. 2.1 months for placebo patients (HR = 0.63; 95% CI, 0.52-0.75).

Although the median OS was not statistically significant, a pre-specified subgroup of patients with an elevated baseline of AFP of at least 400 ng/mL showed a greater survival improvement with ramucirumab treatment, according to the release.

The median time to tumor progression was 3.5 months in the ramucirumab group vs. 2.6 months in the placebo group (HR = 0.59; 95% CI, 0.49-0.72). More patients in the ramucirumab group achieved disease control compared with patients who received placebo (159 vs. 129; P = .011). 

Ten percent of patients in the ramucirumab group discontinued treatment due to adverse events (n = 28) compared with 3% in the placebo group (n = 8). Grade 3 or greater adverse events were similar between the two groups, with the most common being ascites (5% in treated vs. 4% in placebo); hypertension (12% vs. 4%); asthenia (5% vs. 2%); increased aspartate aminotransferase level (5% vs. 8%); thrombocytopenia (5% vs. < 1%); malignant neoplasm progression (6% vs. 4%); hyperbilirubinemia (1%vs. 5%); and increased blood bilirubin (2% vs. 5%).

“Second-line treatment of advanced hepatocellular carcinoma has been an area of high unmet need, and so far no drugs have clearly shown a survival benefit after sorafenib,” the researchers concluded. “Although we failed to demonstrate an improvement in overall survival with the use of ramucirumab after first-line sorafenib, the effects of the drug in patients with elevated baseline alpha-fetoprotein concentrations of 400 ng/mL may warrant further investigation.” – by Melinda Stevens

Disclosures: Zhu reports receiving grants from Eli Lilly during the study. Please see the study for a full list of all other authors’ relevant financial disclosures.