Sorafenib treatment in Child–Pugh A and B patients with advanced hepatocellular carcinoma: safety, efficacy and prognostic factors

163 Background: Available clinical prognostic scoring systems for advanced hepatocellular carcinoma (HCC) were developed in the era of conventional chemotherapy. In 2008, the molecularly targeted agent sorafenib became the new standard of care for advanced HCC due to its survival benefit. The utility of these prognostic models in the setting of sorafenib is unclear. Our aims were to assess for new prognostic factors in patients treated with sorafenib and compare these with known prognostic systems. Methods: All patients diagnosed with advanced HCC from 2008 to 2010 in British Columbia, Canada and treated with sorafenib at any 1 of 5 regional cancer centers were eligible. Based on the established Okuda, CLIP, Barcelona, and French staging systems, we collected baseline demographic and disease characteristics of patients prior to receipt of sorafenib. Multivariate logistic regression models were constructed to examine for associations between these clinical factors and overall survival. Results: Of 183 patients identified, 152 were evaluable: median age was 63 years, 78% were men, average number of sorafenib treatment was 5.3 cycles, and median overall survival was 9.6 months. The prevalence of hepatitis B, hepatitis C, and alcohol-related liver disease were 32%, 15%, and 11%, respectively. Univariate analyses showed that poor performance status, presence of clinical ascites, as well as elevated serum AST, GGT, ALP, bilirubin and platelet levels were each associated with worse overall survival (all p<0.05). In multivariate analyses, however, none of these clinical factors continued to be independently predictive of outcome (all p>0.05). Conclusions: Traditional clinical prognostic factors developed in the era of conventional chemotherapy do not appear to have the same prognostic utility in this contemporary Western cohort of advanced HCC patients treated with sorafenib. This observation underscores the need to identify molecular biomarkers that provide better prognostic information.

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The prognostic factors between different viral etiologies among advanced hepatocellular carcinoma patients receiving sorafenib treatment

Journal of Hepatology ◽

10.1016/s0168-8278(18)30629-9 ◽

2018 ◽

Vol 68 ◽

pp. S208

Author(s):

M.-L. Yeh ◽

J.-F. Huang ◽

M.-L. Yu ◽

C.-Y. Dai ◽

C.-F. Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Factors ◽

Advanced Hepatocellular Carcinoma ◽

Sorafenib Treatment ◽

Viral Etiologies

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Hepatic arterial infusion chemotherapy after sorafenib treatment in patients with advanced hepatocellular carcinoma who are unfit for regorafenib.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.355 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 355-355

Author(s):

Takeshi Terashima ◽

Tatsuya Yamashita ◽

Noboru Takata ◽

Kuniaki Arai ◽

Eishiro Mizukoshi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Hepatic Arterial Infusion ◽

Hepatic Arterial Infusion Chemotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Arterial Infusion ◽

Sorafenib Treatment ◽

Arterial Infusion Chemotherapy ◽

Infusion Chemotherapy

355 Background: The RESORCE trial proved survival benefit of regorafenib on advanced hepatocellular carcinoma (aHCC) in the limiting cohort. This study aimed to investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) as second-line treatment in patients with aHCC who are unfit for regorafenib. Methods: We studied consecutive 159 patients with aHCC treated with sorafenib in our institution from June 2009 to March 2018. We divided them into two groups according to the eligibility for RESORCE trial (Rego or non-Rego group) and investigated the efficacy of HAIC as post-sorafenib treatment. Moreover, we also analyzed the prognostic factors in each group. Results: When sorafenib treatment failed, 63 patients (39.6%) fulfilled key inclusion criteria of the RESORCE trial and were considered as fit for regorafenib treatment (Rego group). Among 96 remaining patients (non-Rego group), 34 patients (35.4%) were treated with HAIC after sorafenib. The objective response and the median progression-free survival of HAIC were 38.2% and 3.9 months, which were independent of the efficacy or treatment duration of sorafenib. The median survival of HAIC after sorafenib was 11.3 months which was significantly longer than that of 62 patients without HAIC (4.7 months; P = 0.023). Four factors, HAIC (HR 0.516), Child-Pugh A (HR 0.362), tumor size ≥35mm (HR 1.959), and AFP ≥200 (HR 1.728), were identified as independent prognostic factors after sorafenib in multivariate analysis. In Rego group, 14 patients were actually treated with regorafenib and their survival after sorafenib was longer than that of the patients without regorafenib and with HAIC (P < 0.01 and P < 0.01, respectively). In Rego group, regorafenib (HR 0.152), extrahepatic lesions (HR 2.160), and ≥10 intra-hepatic lesions (HR 2.099) were identified as prognostic factors after sorafenib in multivariate analysis. Conclusions: HAIC showed promising tumor response and patients’ outcome for the patients who are unfit for regorafenib. Further investigation is needed to compare HAIC with ramucirumab, cabozantinib or nivolumab.

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Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

Digestive Diseases ◽

10.1159/000480257 ◽

2017 ◽

Vol 35 (6) ◽

pp. 611-617 ◽

Cited By ~ 9

Author(s):

Kazuomi Ueshima ◽

Naoshi Nishida ◽

Masatoshi Kudo

Keyword(s):

Hepatocellular Carcinoma ◽

Objective Response ◽

Progression Free Survival ◽

Sequential Therapy ◽

Advanced Hepatocellular Carcinoma ◽

Open Label ◽

Effective Treatment Option ◽

Sorafenib Treatment ◽

Advanced Hcc ◽

Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

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Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03627-1 ◽

2021 ◽

Author(s):

Osman Öcal ◽

Kerstin Schütte ◽

Juozas Kupčinskas ◽

Egidijus Morkunas ◽

Gabija Jurkeviciute ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Objective Response ◽

Advanced Hepatocellular Carcinoma ◽

Sorafenib Treatment ◽

Post Hoc Analysis ◽

Y90 Radioembolization ◽

Baseline Values ◽

Post Hoc

Abstract Purpose To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Methods A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response. Results Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9–8.9], p < 0.001) and IL-8 (HR, 2.4 [1.2–4.7], p = 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22–7.3], p = 0.017) and IL-8 (HR, 2.19 [1.02–4.7], p = 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%, p = 0.007; IL-8, 50.0% vs. 17.4%, p = 0.011). Conclusion IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.

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