Child-Pugh score a prognostic factor for sorafenib response in HCC patients?
Sorafenib appears to be well-tolerated in patients with hepatocellular carcinoma (HCC), with the subgroup of Child-Pugh B patients having a shorter treatment duration and higher serious adverse event (SAE) incidence, according to the results of a subgroup analysis of GIDEON*.
In a cohort of 508 HCC patients who received sorafenib, treatment duration was likely to be shorter among patients with worse Child-Pugh score (17.4 vs 7.6 weeks for Child-Pugh A and B, respectively). Overall, sorafenib treatment lasted for a median of 15.90 weeks, with an average daily dose of 419 mg. [J Gastroenterol 2016;51:1150–1160]
The efficacy endpoint of overall survival was longer among patients with Child-Pugh A than among those with Child-Pugh B (17.4 vs 4.9 months). Time to progression was also better among Child-Pugh A patients, although the difference was not particularly remarkable (3.7 vs 2.3 months).
In terms of safety, the incidence of SAEs and drug-related SAEs was higher in the group of patients with Child-Pugh B than in the group of those with Child-Pugh A (69 vs 37 percent; and 32.8 vs 16.2 percent, respectively). Liver dysfunction and hepatic encephalopathy were the most common drug-related SAEs, followed by gastric ulcer and abnormal laboratory tests.
Treatment discontinuation due to AEs and treatment-emergent death occurred with greater frequency in the Child-Pugh B than in the Child-Pugh A group (51.7 vs 38.7 percent; and 34.5 vs 11.8 percent, respectively).
The median age of the GIDEON cohort was 70 years, and men comprised the majority (80 percent). Of the patients, 85 percent were Child-Pugh A and 11.4 percent were Child-Pugh B.
When the analysis was stratified by geographical area, patients in Japan had the highest incidence of treatment-related AEs—including treatment-related SAEs and AEs leading to permanent discontinuation—but the lowest death rate.
“Japanese patients showed a longer time from initial diagnosis to death than those in other regions. In addition, the median overall survival from the start of sorafenib therapy was longest, but the median time to progression was shorter than in other regions,” researchers noted.
They said the difference could be the consequence of early detection or because there were more treatment opportunities in Japan than in other regions.
“In addition, time to progression from the start of sorafenib therapy in Japanese patients was the shortest among patients worldwide; Japan’s early monitoring by imaging appears to be the major reason why Japanese patients have the shortest time to progression,” they added.
The study may be limited by the lack of a control group or not including a randomization. Despite this, the data highlight the importance of evaluating the individual benefit and risk prior when considering sorafenib treatment for HCC patients with Child-Pugh B.
*Global Investigation of Therapeutic DEcisions in Hepatocellular Carcinoma and Of its Treatment with Sorafenib