RE: Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma

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.

Download Full-text

Abstract No. 4 Accuracy of scout dose Y90 liver biodistribution for personalized treatment planning of Y90 radioembolization of hepatocellular carcinoma: interim analysis of a prospective clinical trial

Journal of Vascular and Interventional Radiology ◽

10.1016/j.jvir.2021.03.415 ◽

2021 ◽

Vol 32 (5) ◽

pp. S3

Author(s):

N. Kokabi ◽

B. Cheng ◽

D. Brandon ◽

Z. Bercu ◽

I. Sethi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Treatment Planning ◽

Interim Analysis ◽

Personalized Treatment ◽

Prospective Clinical Trial ◽

Y90 Radioembolization

Download Full-text

Brivanib in Patients With Advanced Hepatocellular Carcinoma Who Were Intolerant to Sorafenib or for Whom Sorafenib Failed: Results From the Randomized Phase III BRISK-PS Study

Journal of Clinical Oncology ◽

10.1200/jco.2012.47.3009 ◽

2013 ◽

Vol 31 (28) ◽

pp. 3509-3516 ◽

Cited By ~ 359

Author(s):

Josep M. Llovet ◽

Thomas Decaens ◽

Jean-Luc Raoul ◽

Eveline Boucher ◽

Masatoshi Kudo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Growth Factor ◽

Controlled Trial ◽

Objective Response ◽

Phase Iii ◽

Advanced Hepatocellular Carcinoma ◽

Time To Progression ◽

Fibroblast Growth Factor Receptors ◽

Double Blind ◽

Dual Inhibitor

Purpose Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who cannot tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib. Patients and Methods In all, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), and disease control rate based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and safety. Results Median OS was 9.4 months for brivanib and 8.2 months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307). Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2% for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%). Conclusion In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.

Download Full-text

Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma: Preliminary Toxicity and Activity Data in Dogs

Cancers ◽

10.3390/cancers12051272 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1272 ◽

Cited By ~ 1

Author(s):

Laura Marconato ◽

Silvia Sabattini ◽

Giorgia Marisi ◽

Federica Rossi ◽

Vito Ferdinando Leone ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Safety Profile ◽

Median Overall Survival ◽

Response Rate ◽

Treatment Options ◽

Objective Response ◽

Metronomic Chemotherapy ◽

Time To Progression ◽

Activity Data

Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191–535) in dogs treated with sorafenib versus 27 days (95% CI, 0–68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0–909) in dogs receiving sorafenib, while 32 days (95% CI, 0–235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.

Download Full-text

Comparison between Y90 Radioembolization Plus Sorafenib and Y90 Radioembolization alone in the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis

Cancers ◽

10.3390/cancers12040897 ◽

2020 ◽

Vol 12 (4) ◽

pp. 897

Author(s):

Antonio Facciorusso ◽

Irene Bargellini ◽

Marina Cela ◽

Ivan Cincione ◽

Rodolfo Sacco

Keyword(s):

Hepatocellular Carcinoma ◽

Propensity Score ◽

Liver Toxicity ◽

Propensity Score Analysis ◽

Objective Response ◽

Progression Free Survival ◽

Tumor Burden ◽

Y90 Radioembolization ◽

Group 2 ◽

Group 1

Background: Adjuvant sorafenib may enhance the efficacy of transarterial radioembolization with yttrium-90 in hepatocellular carcinoma patients. The aim of this study is to assess the efficacy and safety of radioembolization plus sorafenib in comparison to radioembolization alone. Methods: Out of 175 hepatocellular carcinoma (HCC) patients treated with radioembolization between 2011 and 2018, after propensity score matching, two groups were compared: a group of 45 patients that underwent radioembolization while being on sorafenib (Group 1) and a second group of 90 patients that underwent radioembolization alone (Group 2). Results: Baseline characteristics of the two groups were well balanced concerning liver function and tumor burden. No significant differences in survival outcomes were identified (median overall survival 10 vs. 10 months; p = 0.711), median progression-free survival 6 vs. 7 months (p = 0.992) in Group 1 and Group 2). The objective response rate in Group 1 vs. Group 2 was 45.5% vs. 42.8% (p = 1) according to mRECIST. No differences in toxicity nor in liver decompensation rates were registered. Conclusions: The association of sorafenib does not prolong survival nor delay progression in patients treated with radioembolization. Liver toxicity does not differ among the two therapeutic schemes.

Download Full-text