A Single-Institute Experience with Sorafenib in Untreated and Previously Treated Patients with Advanced Hepatocellular Carcinoma

Introduction. Hepatitis C is the first major cause for HCC in Morocco. Antiviral treatment reduces the risk of developing HCC but few cases of HCC in HCV-treated patients were reported. We aimed to define this population’s features and to identify predictive factors of developing HCC. Patients and Methods. We included all HCV carriers who developed HCC after antiviral treatment from January 2002 to April 2010. We compare HCV-treated patients with no developed HCC to HCC population using khi-2 and Fisher Exact analysis. Results. 369 HVC-treated patients were considered, and 20 HCC were reported. The risk of HCC was not significant according to gender and genotypes (resp., P=0.63 and P=0.87). Advanced age and severe fibrosis were significant risk factors (resp., P=0.003 and P=0.0001). HCC was reported in 2.6% of sustained virological responders versus 12.5% of nonresponders (P=0.004). Conclusion. In our series, 5% of previously treated patients developed an HCC. Advanced age and severe fibrosis at HCV diagnosis are predictive factors of HCC occurrence. Sustained virological response reduces considerably the risk of HCC occurrence but screening is indicated even after SVR.

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Prognostic and predictive factors from the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (aHCC)

Annals of Oncology ◽

10.1093/annonc/mdz422.011 ◽

2019 ◽

Vol 30 ◽

pp. ix48

Author(s):

T. Yau ◽

T. Meyer ◽

R.K. Kelley ◽

M. Mangeshkar ◽

A.-L. Cheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Predictive Factors ◽

Phase Iii ◽

Advanced Hepatocellular Carcinoma ◽

Previously Treated ◽

Prognostic And Predictive Factors

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Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial

The Lancet Oncology ◽

10.1016/s1470-2045(20)30011-5 ◽

2020 ◽

Vol 21 (4) ◽

pp. 571-580 ◽

Cited By ~ 33

Author(s):

Shukui Qin ◽

Zhenggang Ren ◽

Zhiqiang Meng ◽

Zhendong Chen ◽

Xiaoli Chai ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Advanced Hepatocellular Carcinoma ◽

Phase 2 ◽

Open Label ◽

Phase 2 Trial ◽

Parallel Group ◽

Previously Treated

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Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial

Journal of Clinical Oncology ◽

10.1200/jco.19.01307 ◽

2020 ◽

Vol 38 (3) ◽

pp. 193-202 ◽

Cited By ~ 144

Author(s):

Richard S. Finn ◽

Baek-Yeol Ryoo ◽

Philippe Merle ◽

Masatoshi Kudo ◽

Mohamed Bouattour ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Interim Analysis ◽

Statistical Significance ◽

Study Drug ◽

Progression Free Survival ◽

Final Analysis ◽

Phase Iii ◽

Advanced Hepatocellular Carcinoma ◽

Double Blind ◽

Previously Treated

PURPOSE Pembrolizumab demonstrated antitumor activity and safety in the phase II KEYNOTE-224 trial in previously treated patients with advanced hepatocellular carcinoma (HCC). KEYNOTE-240 evaluated the efficacy and safety of pembrolizumab in this population. PATIENTS AND METHODS This randomized, double-blind, phase III study was conducted at 119 medical centers in 27 countries. Eligible patients with advanced HCC, previously treated with sorafenib, were randomly assigned at a two-to-one ratio to receive pembrolizumab plus best supportive care (BSC) or placebo plus BSC. Primary end points were overall survival (OS) and progression-free survival (PFS; one-sided significance thresholds, P = .0174 [final analysis] and P = .002 [first interim analysis], respectively). Safety was assessed in all patients who received ≥ 1 dose of study drug. RESULTS Between May 31, 2016, and November 23, 2017, 413 patients were randomly assigned. As of January 2, 2019, median follow-up was 13.8 months for pembrolizumab and 10.6 months for placebo. Median OS was 13.9 months (95% CI, 11.6 to 16.0 months) for pembrolizumab versus 10.6 months (95% CI, 8.3 to 13.5 months) for placebo (hazard ratio [HR], 0.781; 95% CI, 0.611 to 0.998; P = .0238). Median PFS for pembrolizumab was 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 2.5 to 4.1 months) for placebo at the first interim analysis (HR, 0.775; 95% CI, 0.609 to 0.987; P = .0186) and 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 1.6 to 3.0 months) at final analysis (HR, 0.718; 95% CI, 0.570 to 0.904; P = .0022). Grade 3 or higher adverse events occurred in 147 (52.7%) and 62 patients (46.3%) for pembrolizumab versus placebo; those that were treatment related occurred in 52 (18.6%) and 10 patients (7.5%), respectively. No hepatitis C or B flares were identified. CONCLUSION In this study, OS and PFS did not reach statistical significance per specified criteria. The results are consistent with those of KEYNOTE-224, supporting a favorable risk-to-benefit ratio for pembrolizumab in this population.

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KEYNOTE-224: Phase II study of pembrolizumab in patients with previously treated advanced hepatocellular carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.tps504 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. TPS504-TPS504 ◽

Cited By ~ 7

Author(s):

Andrew X. Zhu ◽

Jennifer J. Knox ◽

Masatoshi Kudo ◽

Stephen L. Chan ◽

Richard S. Finn ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Disease Progression ◽

Kinase Inhibitor ◽

Performance Status ◽

Objective Response ◽

Progression Free Survival ◽

Locoregional Therapy ◽

Advanced Hepatocellular Carcinoma ◽

Ecog Performance Status ◽

Previously Treated

TPS504 Background: The tyrosine kinase inhibitor sorafenib is the standard of care for first-line hepatocellular carcinoma (HCC). For patients with HCC after disease progression on sorafenib or for those with intolerance to sorafenib, no approved therapies are available. Because HCC is often driven by inflammation and is also associated with a suppressed immunoenvironment, there is a strong rationale to evaluate immunotherapy in patients with this type of cancer. The single-arm, multisite, phase 2 KEYNOTE-224 study (ClinicalTrials.gov, NCT02702414) was designed to evaluate the efficacy and safety of the anti–PD-1 antibody pembrolizumab in patients with previously treated advanced HCC. Methods: Approximately 100 patients will be enrolled. Inclusion criteria include age ≥18 years, histologically or cytologically confirmed diagnosis of HCC Barcelona Clinic Liver Cancer (BCLC) stage C disease or BCLC stage B disease not amenable to or refractory to locoregional therapy, and disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation). Patients must also have measurable disease based on RECIST v1.1 as confirmed by central imaging vendor review, documented objective radiographic progression after stopping treatment with sorafenib or intolerance to sorafenib, Child-Pugh liver score A, ECOG performance status 0-1, and predicted life expectancy > 3 months. Patients will be allocated to receive pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles (~2 years) or until disease progression, unacceptable toxicity, patient withdrawal of consent, or investigator decision. Response will be assessed every 9 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. The primary end point is objective response rate per RECIST v1.1 by central imaging vendor review. Secondary end points are overall survival; safety and tolerability; and duration of response, disease control rate, time to progression, and progression-free survival per RECIST v1.1 by central imaging vendor review. Enrollment in KEYNOTE-224 is ongoing. Clinical trial information: NCT02702414.

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