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Second-Line Ramucirumab in Advanced HCC


In an exploratory analysis of the REACH trial in advanced hepatocellular carcinoma reported in JAMA Oncology, Andrew X. Zhu, MD, PhD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, and colleagues found a borderline survival benefit of second-line ramucirumab (Cyramza) vs placebo among patients with a Child-Pugh score of 5 and a significant benefit among patients with a Child-Pugh score of 5 or 6 and an alpha-fetoprotein level ≥ 400 ng/mL. Ramucirumab is a human vascular endothelial factor receptor 2 antagonist.

In the phase III REACH trial, ramucirumab was not associated with a significant overall survival benefit overall among patients with Child-Pugh class A (scores 5 and 6) disease who had received first-line sorafenib (Nexavar). Subgroup analysis indicated improved overall survival with ramucirumab among patients with a baseline alpha-fetoprotein level ≥ 400 ng/mL.

The current analysis according to Child-Pugh score included all 643 randomized patients: 565 with Child-Pugh class A disease (Child-Pugh scores 5 [n = 357] and 6 [n = 208]) and 78 patients with class B disease (scores 7 and 8 [n = 78]).

Overall Survival

Among all patients with a Child-Pugh score of 5, ramucirumab was associated with a borderline overall survival benefit vs placebo (hazard ratio [HR] = 0.80, P = .06); no benefit was observed among patients with Child-Pugh scores of 6 (HR = 0.96, P = .76) or 7 and 8 (HR = 1.00, P = > .99). Among patients with alpha-fetoprotein levels ≥ 400 ng/mL, ramucirumab was associated with an overall survival benefit among 151 patients with a Child-Pugh score of 5 (HR = 0.61, P = .01) and 100 patients with a Child-Pugh score of 6 (HR = 0.64, P = .04) but not among 39 patients with scores of 7 and 8.

Grade ≥ 3 adverse events, including ascites and asthenia, were more common in patients with a Child-Pugh score of 7 and 8 vs 5 and 6 irrespective of treatment group.

The investigators concluded: “In unselected patients, a trend for ramucirumab survival benefit was observed only for patients with a Child-Pugh score of 5. In patients with baseline [alpha-fetoprotein] levels of 400 ng/mL or more, a ramucirumab survival benefit was observed for Child-Pugh scores of 5 and 6. Ramucirumab had a manageable toxic effect profile. These results support the ongoing REACH-2 study of ramucirumab in patients with advanced [hepatocellular carcinoma] with underlying Child-Pugh A cirrhosis and baseline [alpha-fetoprotein] levels of 400 ng/mL or more.”

The study was supported by Eli Lilly and Company. ■

Zhu AX, et al: JAMA Oncol. September 22, 2016 (early release online).



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