Mo1055 Clinical Features Associated With Radiological Response to Sorafenib Therapy for Unresectable Hepatocellular Carcinoma; A Multicenter Study in Japan

Abstract

Background and Aim: There has been no established biomarker to predict clinical response to sorafenib. The aim of this study is to investigate predictive factors associated with radiological response to sorafenib therapy for Japanese patients with unresectable hepatocellular carcinoma (HCC). Method: A total of 465 patients with unresectable HCC were treated with sorafenib in our fourteen hospitals in Japan before August 2013. Among them, 316 patients with sufficient available clinical data were included in this study.We analyzed the relationship between radiological response and clinicopathological factors including age, sex, performance status, liver function, tumor status such as portal invasion and serum AFP decrease during the first one month, and examined the predictive factors for the favorable responder to sorafenib therapy. Furthermore, we performed tumor biopsy prior to sorafenib therapy in 62 patients, and investigated the relationship between tumor differentiation degree and radiological response. Results: Study population consisted of 259 males and 57 females with a median age of 70 years (range, 37-90 years). Of these, 191 patients (60.4%) were classified with BCLC stage C, and 271 patients (85.8%) had liver function of Child-Pugh A. Median overall survival and progression free survival were 289 and 98 days. Regarding the best tumor response evaluated by modified RECIST, number of CR/ PR/ SD/ PD were 4/ 51/ 136/ 125, respectively. In a multivariate analysis, female (p = 0.001, odds ratio = 3.018, 95% confidence interval (CI); 1.540-5.915) and AFP decrease (p = 0.014, odds ratio = 2.146, 95% CI; 1.170-3.922) were the independent predictors linked to objective tumor response (CR or PR). Regarding the background of female patients, females were elder (p = 0.007) with lower body weight (p < 0.001) than males and tended to be given reduced initial dose of sorafenib (p = 0.081). Their mean initial dosage of sorafenib per kg was less than males (7.2 vs. 8.5 mg/kg, p = 0.013). As for any adverse events and administration period of sorafenib, no difference in genders was found. In 62 patients with tumor biopsy samples, disease control rate (DCR) of patients with well differentiated HCC was significantly higher than the others (80% vs. 45.9%, p = 0.009). Conclusion: Serum AFP decrease in the first one month was associated with radiological response as previously reported. In addition, our results suggested that female would be one of the independent predictors for favorable response to sorafenib. In histological examination, well differentiated HCC was associated with favorable disease control. Further investigations with regard to biomarkers predicting the clinical response to sorafenib in HCC patients are warranted.