In patients with advanced hepatocellular carcinoma (HCC) and a baseline α-fetoprotein (αFP) level of 400 ng/mL or more, a survival benefit with second-line ramucirumab therapy was observed for those with Child-Pugh scores of 5 and 6, according to a secondary analysis published in JAMA Oncology.1
The phase 3 REACH trial (A Study of Ramucirumab [IMC-1121B] Drug Product and Best Supportive Care (BSC) Versus Placebo and BSC as Second-Line Treatment in Participants With Hepatocellular Carcinoma After First-Line Therapy With Sorafenib; ClinicalTrials.gov Identifier: NCT01140347) demonstrated a significant difference in progression-free survival between ramucirumab plus best supportive care and placebo plus best supportive care; however, there was no significant difference in overall survival between these 2 treatment arms in unselected patients.
Therefore, researchers sought to evaluate the clinical outcomes associated with post-sorafenib ramucirumab treatment with respect to severity of liver disease and baseline αFP levels.
Results demonstrated a trend toward an overall survival benefit with ramucirumab only for patients with a Child-Pugh score of 5 (hazard ratio [HR], 0.80; 95% CI, 0.63-1.02; P =.06), but no apparent for those with Child-Pugh scores of 6 or 7 and 8.
Researchers found that in patients with baseline αFP levels of 400 ng/mL or greater, a significant survival benefit with ramucirumab was observed for patients with a Child-Pugh score of 5 and 6. Specifically, patients with a Child-Pugh score of 5 had a 39% reduced risk of death (HR, 0.61; 95% CI, 0.43-0.87; P =.01) and those with Child-Pugh 6 had a 36% reduction in the risk of death (HR, 0.64; 95% CI, 0.42-0.98; P =.04) with ramucirumab.
However, there was no significant association between ramucirumab treatment and overall survival for those with Child-Pugh 7 and 8 and baseline αFP levels of 400 ng/mL or more.
In terms of safety, the toxicity profile of ramucirumab was deemed manageable regardless of Child-Pugh score, but patients with Child-Pugh scores of 7 and 8 reported a higher incidence of grade 3 or worse treatment-emergent adverse events in both the ramucirumab and placebo arms compared with those with Child-Pugh scores of 5 or 6.
Ultimately, these findings support the ongoing REACH-2 study (ClinicalTrials.gov Identifier: NCT02435433), which is evaluating ramucirumab compared with placebo in patients with HCC and elevated baseline αFP levels.
1. Zhu AX, Baron AD, Malfertheiner P, et al. Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Analysis of REACH trial results by Child-Pugh score. JAMA Oncol. 2016 Sep 22. doi: 10.1001/jamaoncol.2016.4115. [Epub ahead of print]