Differential Response to Sorafenib Administration for Advanced Hepatocellular Carcinoma

Abstract

Sorafenib has been used to treat advanced hepatocellular carcinoma (aHCC). However, there is no evidence for a response of different target lesions to sorafenib administration. Therefore, we aimed to evaluate the effect of sorafenib on various aHCC target lesions. The outcomes of sorafenib treatment on aHCC, i.e., treatment response for all Child A status patients receiving the drug, were analyzed. Of 377 aHCC patients, 73 (19.3%) had complete/partial response to sorafenib, while 134 (35.4%) and 171 (45.2) had a stable or progressive disease, respectively, in the first six months. Of the evaluated metastatic lesions, 149 (39.4%), 48 (12.7%), 123 (32.5%), 98 (25.9%), 83 (22.0%), and 45 (11.9%) were present in liver, bone, lung, portal/hepatic vein thrombus, lymph nodes, and peritoneum, respectively. The overall survival and duration of treatment were 16.9 ± 18.3 and 8.1 ± 10.5 months (with median times of 11.4 and 4.6, respectively). Our analysis showed poor outcomes in macroscopic venous thrombus and bone, higher AFP, and multiple target lesions. ALBI grade A had a better outcome. Sorafenib administration showed good treatment outcomes in selected situations. PD patients with thrombus or multiple metastases should be considered for sorafenib second-line treatment. The ALBI liver function test should be selected as a treatment criterion.

Prognostic impact of metastatic site in patients receiving first-line sorafenib therapy for advanced hepatocellular carcinoma

“…Regarding the actual impact of different sites of metastases on prognosis, evidence is scarce, and results are often contradictory. Two recently published works on this topic are the study of Zhan H et al, based on the American epidemiologic registry SEER (Surveillance, Epidemiology and End Results) that gives OS results [24], and the study of Huang SF et al, based on the national registry of Taiwan that gives PFS results [25]. In the first study, lymph nodes were not considered as a metastatic site, and less than a half of patients were on systemic treatment; in the second study all patients with advanced HCC were analyzed, including those without EHS.…”

Small molecule tyrosine kinase inhibitors approved for systemic therapy of advanced hepatocellular carcinoma: recent advances and future perspectives

“…In aHCC patients with various organ lesions (n = 377), sorafenib had a median OS, ORR, and DCR of 11.4 months, 19.4%, and 54.7% respectively. Patients with bone metastasis, lung metastasis, macrovascular invasion (MVI) or multiple lesions had significantly worse PFS compared with those without corresponding lesion(s) (P = 0.021, 0.036, 0.038, and 0.009, respectively) [ 23 ]. Compared with patients enrolled in SHARP [ 19 ], Asia–Pacific [ 20 ], and HATT [ 22 ] trials, patients in this study had numerically better OS and tumor responses.…”

Role of reimbursement and Physicians' awareness in the survival of sorafenib‐eligible advanced hepatocellular carcinoma patients

“…Since its approval in 2008, numerous studies have investigated sorafenib's pharmacological mechanisms and survival outcomes. 20,21 However, to date, there has been relatively limited literature discussing the impact of national healthcare policies, particularly national health insurance, on survival outcomes. In this study, we examined the survival benefits of individuals receiving reimbursed treatment with sorafenib from the perspective of national healthcare policies.…”

“…Since its approval in 2008, numerous studies have investigated sorafenib's pharmacological mechanisms and survival outcomes 20,21 . However, to date, there has been relatively limited literature discussing the impact of national healthcare policies, particularly national health insurance, on survival outcomes.…”