scholarly journals Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

2019 ◽  
Author(s):  
Oronzo Brunetti ◽  
Antonio Gnoni ◽  
Antonella Licchetta ◽  
Vito Longo ◽  
Angela Calabrese ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Prognostic Markers ◽  
Kinase Inhibitor ◽  
Quality Standard ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
First Line ◽  
Advanced Hcc ◽  
First Line Treatment

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, currently predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

scholarly journals Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 707 ◽  
Author(s):  
Oronzo Brunetti ◽  
Antonio Gnoni ◽  
Antonella Licchetta ◽  
Vito Longo ◽  
Angela Calabrese ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Prognostic Markers ◽  
Kinase Inhibitor ◽  
Quality Standard ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
First Line ◽  
Advanced Hcc ◽  
First Line Treatment

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

scholarly journals Non-immunotherapy options for the first-line management of hepatocellular carcinoma: exploring the evolving role of sorafenib and lenvatinib in advanced disease

2020 ◽  
Vol 27 (S3) ◽  
Author(s):  
S. Perera ◽  
D. Kelly ◽  
G. M. O'Kane
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Optimal Timing ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment ◽  
Line Management

 The results of the sharp trial established sorafenib, a tyrosine kinase inhibitor (TKI), as the sole first-line treatment option in advanced hepatocellular carcinoma (HCC) for more than a decade. In 2020, there has been a surge in new therapies for hcc, including immunotherapeutic strategies and the approval of a number of novel tkis. In addition to sorafenib, lenvatinib and combination atezolizumab–bevacizumab now represent standard first-line treatment options. As those systemic options begin to be better utilized, assurance of adequate liver function and optimal timing are required to improve patient outcomes. Furthermore, sequencing of the agents will have to be carefully tailored, given the increasing armamentarium of choices. Here, we discuss the role of lenvatinib and sorafenib in the first-line management of HCC.  

Association of hypothyroidism with improved outcomes in first-line treatment of renal cell carcinoma with sunitinib.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 466-466 ◽  
Author(s):  
Flavio Augusto Ismael Pinto ◽  
Augusto Akikubo Rodrigues Pereira ◽  
Maria Nirvana Formiga ◽  
Marcello Ferretti Fanelli ◽  
Ludmilla T. D. Chinen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Univariate Analysis ◽  
Intermediate Risk ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

466 Background: Sunitinib, a multitarget tyrosine-kinase inhibitor, has become a standard of care for first-line low and intermediate risk metastatic renal cell carcinoma (mRCC). Sunitinib-induced hypothyroidism and hypertension have been correlated with better outcomes in those patients. Methods: Fifty patients with mRCC, treated in the first-line with sunitinib, were retrospective analyzed at one brazilian institution, for overall survival (OS), progression free survival (PFS), overall response rate (ORR) and toxicity. We evaluated clinical and laboratory parameters, such as hypothyroidism (TSH level > 5,5 mIU/L) and hypertension, to identify prognostic factors. Results: The median age of patients was 58 years (range: 37-73 years), 82% were male, 54% were ECOG 0 or 1, and 76% were classified in low or intermediate risk. Nefrectomy was performed in 96% of cases. Lung and bone were the most common sites of metastases. The incidence of hypothyroidism and hypertension during treatment were 40% and 34%, respectively. ORR for the entire population was 40% and it was statistically superior in patients that developed hypothyroidism during treatment (90% vs. 20%; p<0,0001). Median survival and PFS were 21.7 months (10.65-17.70 months, 95% CI) and 14.2 months (15.77-27.58 months, 95% CI), respectively. In univariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001), hypothyroidism (p<00001) and hypertension (p=0,001) were associated with OS. In multivariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001) and hypothyroidism (p<00001) were independent prognostic factors for OS. The most common severe adverse events (G3-4) were asthenia (14%), diarrhoea (6%), neutropenia (14%), thrombocytopenia (10%), hand-foot syndrome (6%) and hypertension (8%). Conclusions: Efficacy in survival and toxicity profile of sunitinib in first-line treatment of mRCC in patients out of clinical trials were comparable to prior studies. Hypothyroidism, MSKCC criteria and ECOG were independent prognostic factors for survival.

Phase Ib study of regorafenib (REG) plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 564-564 ◽  
Author(s):  
Anthony B. El-Khoueiry ◽  
Richard D. Kim ◽  
William P. Harris ◽  
Max W. Sung ◽  
Dirk Waldschmidt ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Synergistic Effects ◽  
Immunomodulatory Activity ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Dose Escalation Study ◽  
Advanced Hcc ◽  
First Line Treatment

564 Background: REG is a multikinase inhibitor with immunomodulatory activity and PEMBRO is an anti-PD-1 monoclonal antibody. Both are approved as monotherapy for patients (pts) with HCC previously treated with sorafenib. Based on their potential synergistic effects, we conducted a phase 1b study of REG plus PEMBRO for first-line treatment of advanced HCC. Methods: This is an ongoing, open-label, dose-escalation study in pts with advanced HCC who had no prior systemic therapy. In the first cohort, pts received REG 120 mg/day PO for 3 weeks on/1 week off plus PEMBRO 200 mg IV q 3 weeks. In later cohorts, the REG dose could be escalated (160 mg) or reduced (80 mg) based on the modified toxicity probability interval design; the PEMBRO dose is fixed. The primary objective is safety and tolerability. Secondary objectives are to define the maximum tolerated dose (MTD) and recommended phase 2 dose, and to assess antitumor activity. Results: As of August 23, 2019, 29 pts have been treated at the REG 120 mg level. Median age is 65 years (range 32–81); 41%/55% of pts are BCLC stage B/C; 100% are Child–Pugh A; ECOG status 0/1 is 72%/28%. Dose-limiting toxicities occurred in 4/18 evaluable pts: grade (Gr) 3 increased ALT/AST with Gr 2 increased bilirubin (n = 2); Gr 3 rash (n = 2). The MTD of REG in the combination was 120 mg. Most common Gr 3 or 4 treatment-emergent adverse events (TEAEs) are shown (n = 29). There were no Gr 5 TEAEs. 59%/31% of pts had REG/PEMRO-related Gr 3 or 4 TEAEs. Dose modifications (reductions or interruptions) of REG/PEMBRO for drug-related TEAEs occurred in 59%/31% of pts. Of 23 evaluable pts, 7 (30%) had a partial response (PR) and 14 (61%) had stable disease (RECIST v1.1); 1 additional pt had PR by mRECIST. Conclusions: The combination of REG plus PEMBRO for first-line treatment of advanced HCC showed no unexpected safety signals and encouraging antitumor activity. Accrual is continuing at REG 120 mg dose and an expansion cohort evaluating REG 80 mg plus PEMBRO is planned. Clinical trial information: NCT03347292. [Table: see text]

A phase 2 and biomarker study of sorafenib combined with FOLFOX in patients with advanced hepatocellular carcinoma (HCC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 270-270
Author(s):  
Lipika Goyal ◽  
Hui Zheng ◽  
Thomas Adam Abrams ◽  
Rebecca A. Miksad ◽  
Andrea J. Bullock ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Disease Rate ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Phase 2 ◽  
First Line ◽  
Advanced Hcc ◽  
Biomarker Analysis ◽  
First Line Treatment

270 Background: Sorafenib is the standard first line treatment for advanced HCC and showed a median time to progression (TTP) of 5.5 months and an overall response rate (ORR) of 2% in the phase III SHARP trial. FOLFOX has shown modest activity in HCC with a progression free survival (PFS) of 2.9 months and ORR of 8% in a phase III trial. In this single-arm, multicenter phase 2 and biomarker study, sorafenib plus FOLFOX was evaluated in the first line treatment of advanced HCC. Methods: Patients with histologically proven advanced HCC, Child Pugh A liver function, and no prior systemic therapies received sorafenib 400mg orally twice daily during a 2-week lead-in, followed by concurrent modified FOLFOX (5-FUCI 1200mg/m2/day for 46 hours and LV 400mg/m2 bolus, Oxaliplatin 85mg/m2) on day 1 and 15 of each 28-day cycle. The primary endpoint was TTP, calculated from date of study entry to date of radiological or clinical disease progression. Serial plasma anti-angiogenic and anti-inflammatory biomarkers were evaluated. Results: The study enrolled 40 patients with advanced HCC: median age, 65 years; male 85%; Child Pugh A5, 70%; BCLC stage C, 95%; HCC etiology, HCV 40%, HBV 13%, alcohol 13%. Grade 3/4 adverse events were notable for AST (23%), ALT (15%), bilirubin (10%), diarrhea (10%), anemia (10%), hypertension (5%), hand-foot syndrome (5%), and thrombocytopenia (5%). Dose reductions for sorafenib and FOLFOX were done in 73% and 65% of patients, respectively. The median TTP was 8.8 months (95%CI, 6.5-11.2). The ORR was 18%, and the stable disease rate was 55%. Among 36 patients with a baseline AFP ≥ 5 ng/mL, 10 (28%) had a ≥ 50% drop in AFP. Low baseline plasma levels of sVEGFR1, VEGF-C, and bFGF and high levels of s-cMET and IL-12 tended to associate with longer TTP (p < 0.10). Decreased s-cMET at day 15 and decreased s-cMET and IL-2 at day 43 were associated with longer TTP (p < 0.05). Conclusions: Sorafenib+FOLFOX demonstrated encouraging clinical efficacy with moderate toxicity in the first line treatment of advanced HCC. Initial biomarker evaluation suggested a correlation between TTP and baseline angiogenic markers as well as changes in IL-2 and s-cMET. Complete biomarker analysis will be presented at the meeting. Clinical trial information: NCT01775501.

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline

2020 ◽  
Vol 38 (36) ◽  
pp. 4317-4345 ◽  
Author(s):  
John D. Gordan ◽  
Erin B. Kennedy ◽  
Ghassan K. Abou-Alfa ◽  
Muhammad Shaalan Beg ◽  
Steven T. Brower ◽  
...  
Keyword(s):  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Advanced Hcc ◽  
First Line Therapy ◽  
Line Therapy ◽  
First Line Treatment

PURPOSE To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC). METHODS ASCO convened an Expert Panel to conduct a systematic review of published phase III randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and provide recommended care options for this patient population. RESULTS Nine phase III randomized controlled trials met the inclusion criteria. RECOMMENDATIONS Atezolizumab + bevacizumab (atezo + bev) may be offered as first-line treatment of most patients with advanced HCC, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1, and following management of esophageal varices, when present, according to institutional guidelines. Where there are contraindications to atezolizumab and/or bevacizumab, tyrosine kinase inhibitors sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC, Child-Pugh class A liver disease, and ECOG PS 0-1. Following first-line treatment with atezo + bev, and until better data are available, second-line therapy with a tyrosine kinase inhibitor may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with α-fetoprotein ≥ 400 ng/mL), or atezo + bev where patients did not have access to this option as first-line therapy. Pembrolizumab or nivolumab are also reasonable options for appropriate patients following sorafenib or lenvatinib. Consideration of nivolumab + ipilimumab as an option for second-line therapy and third-line therapy is discussed. Further guidance on choosing between therapy options is included within the guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

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