Select HCC patients may benefit from second-line ramucirumab
medwireNews: Chronic liver disease severity and pretreatment α-fetoprotein (αFP) levels could help to identify hepatocellular carcinoma (HCC) patients who may benefit from second-line treatment with ramucirumab, suggests an exploratory analysis of the REACH trial.
The primary analysis of the phase III trial comparing ramucirumab with placebo, both given alongside best supportive care, was restricted to HCC patients with a Child-Pugh score of 5 or 6. Overall survival (OS) was comparable for the treatment arms, but administration of the anti-VEGFR-2 antibody significantly prolonged OS in the subgroup of patients with baseline αFP levels of at least 400 ng/mL.
To explore the potential predictive value of αFP levels and the role of chronic liver disease, the researchers included in the current analysis not just participants with Child-Pugh scores of 5 or 6, but also 7 and 8, who had been eligible for the REACH trial until a protocol modification.
Among 290 patients with baseline αFP levels of 400 ng/mL or higher, ramucirumab accorded a significant OS benefit to those with a Child-Pugh score of 5 or 6 relative to placebo, with hazard ratios of 0.61 and 0.64, respectively. The corresponding median OS times were 8.61 versus 4.76 months and 5.72 versus 3.61 months.
In patients with a Child-Pugh score of 7 and 8, there was a trend towards improved OS with ramucirumab, but the difference did not reach statistical significance.
Moreover, ramucirumab did not significantly extend OS for patients with any Child-Pugh score if they also had baseline αFP levels lower than 400 ng/mL (n=344).
Andrew Zhu (Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, USA) and co-researchers note that “[t]he overall safety profile of ramucirumab, regardless of Child-Pugh score, was considered manageable.”
However, the incidence of grade 3 or worse treatment-emergent adverse events, including ascites and asthenia, as well as toxicities of special interest, such as liver injury and/or failure, was higher in participants with Child-Pugh scores of 7 and 8 versus 5 or 6, regardless of treatment arm.
These differences “are likely related to the more severe liver dysfunction and cirrhosis in patients with higher Child-Pugh scores”, Zhu et al write in JAMA Oncology.
And they conclude: “These results support the ongoing REACH-2 study of ramucirumab in patients with advanced HCC with underlying Child-Pugh A [score of 5 or 6] cirrhosis and baseline αFP levels of 400 ng/mL or more.”
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