Sorafenib in patients with hepatocellular carcinoma: 10 years of real life

Abstract

Introduction: Hepatocellular carcinoma (HCC) is themost common primary malignancy of the liver and the second leading cause of cancer‐related mortality worldwide. Its incidence and prevalence are increasing, especially in some parts of the world. When diagnosed at an advanced stage, the prognosis is poor and approved treatment options are limited. Sorafenib, an oralmulti‐tyrosine kinase inhibitor (VEGFR‐1/2/3, PDGFR, Flt3, c‐Kit, Raf kinases), has been established as the standard of care for patients with advancedHCC since 2007, on the basis of two landmark trials (SHARP andAsia‐Pacific). Although its efficacy is not a matter of doubt, this drug is effective only in a proportion of patients and may cause adverse effects that negatively impact on patient quality of life. Ten years have already passed since sorafenib was introduced in healthcare practice and, despite a lot of research in the field, no validated prognosticmarkers are available for patients treated with this therapeutic agent. Moreover, much of what we know comes fromsub‐analyses and pooled analyses of randomized controlled trials, rather than fromreal life. Therefore, we conducted a fieldpractice study aimed at identifyingwhich baseline factors are associated with overall survival (OS) of patients affected byHCC and treated with sorafenib. Methods: Three hundred and ninety‐eight patients with HCC consecutively treated with sorafenib twice daily between March 2008 and December 2018 were included in the study. For every patient we collected 37 biological/clinical parameters the day before the start of the treatment. OS was estimated by the Kaplan‐Meier method and curves were compared by the log‐rank test. Unadjusted and adjusted hazard ratios (HRs) by baseline characteristics were calculated using the Cox proportional hazards model. Results: Based on univariate analysis, AFP(> 400 vs<400; HR 1.51; P=.0066), albumin(< 35 vs>35; HR 1.47; P= .03), AST(> 40 vs<40; HR 1.92; P= .001), bilirubin(> 1.2 vs 0 vs 0;HR 1.71; P< .0001), SII(>360 vs<360; HR 1.36; P= .04), ALBI grade (1 vs 2; HR 2.47; P= .0008) and portal vein thrombosis (yes vs no; HR 1.45; P= .0065) were significantly associated with a shorter OS. Following adjustment for clinical covariates positive in univariate analysis, the multivariate analysis including AFP (cut‐off 400), age (> or<70 years), aetiology (HBV, HCV and others), albumin (> or < NV), AST (> or or < NV), Child Pugh (A vs B), LDH as a continuous variable, PLR (> or<16), ECOG (0 vs>0), ALBI grade (1 vs 2), portal vein thrombosis (yes vs. no), SII (< 360 vs>360), BCLC stage (B vs C), identified increase of LDH, age> 70 years, other aetiologies, ECOG> 0, albumin 40, were identified as prognostic factors for poorer OS based on the 5% significance level. Conclusion: Our study highlights that hepatic function (ALBI grade, AST, albumin, LDH), patient‐centered variables (ECOG, age) and aetiology, rather than immune inflammation indicators, AFP or tumor stage, have prognostic value. Our study provides insights into the impact of baseline characteristics on the OS of sorafenib‐treated HCC patients in real‐life usual care. This information might have implications in terms of therapeutic decision‐making and patient counseling.