Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies

Bruix, Jordi; Cheng, Ann‐Lii; Meinhardt, Gerold; Nakajima, Keiko; Sanctis, Yoriko De; Llovet, Josep M.

doi:10.1016/j.jhep.2017.06.026

Cited by 496 publications

(459 citation statements)

References 45 publications

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“…Notably, this clinical course is in line with data from the CheckMate 040 trial [9], where responses occurred early in treatment and were long-lasting (median duration of response 17 months). Only recently, different groups identified the presence of HCV as a positive predictor for sorafenib efficacy in patients with HCC [12]. In line with this, we initiated a first-line therapy with sorafenib in our patient suffering from HCV-related liver cirrhosis.…”

Section: Discussion/conclusionmentioning

confidence: 72%

Excellent Response to Anti-PD-1 Therapy in a Patient with Hepatocellular Carcinoma Intolerant to Sorafenib

et al. 2019

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Background: Hepatocellular carcinoma (HCC) represents the most common primary carcinoma of the liver. Most patients present with advanced or metastatic HCC at diagnosis and face a very limited prognosis. Systemic treatment with the tyrosine-kinase inhibitors sorafenib or lenvatinib is considered as the treatment of choice in these patients. In patients intolerant to tyrosine-kinase inhibitors, no standard therapy is approved so far, but several agents have demonstrated efficacy in clinical trials. As such, the checkpoint inhibitors nivolumab and pembrolizumab have been shown to induce tumor response and to prolong survival in patients with advanced HCC, both when intolerant to sorafenib or after failure of a first-line therapy with sorafenib. Case Report: We here report the case of a patient with advanced HCC that demonstrated severe toxicity upon first-line treatment with sorafenib. Administration of sorafenib was discontinued and after careful consideration the patient started a second-line treatment with the PD-1 antibody nivolumab. Strikingly, this treatment led to a significant regression of tumor size and a drastic reduction of alpha-fetoprotein serum concentrations. At 17 months after initiation of treatment, the patient is still alive in excellent condition with sustained tumor response. Conclusion: In summary, we report on a very rare case of a patient with HCC demonstrating an almost complete response to checkpoint inhibitor treatment.

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Section: Discussion/conclusionmentioning

confidence: 72%

Excellent Response to Anti-PD-1 Therapy in a Patient with Hepatocellular Carcinoma Intolerant to Sorafenib

et al. 2019

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“…Finally, as sorafenib treatment is expensive, its associated cost represents a limitation [5]. Although several studies have investigated predictive biomarkers of sorafenib efficacy, there have been no established predictive biomarkers [6-9]. Therefore, a simple biomarker for the prediction of sorafenib efficacy would be clinically advantageous.…”

Section: Introductionmentioning

confidence: 99%

No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma

et al. 2018

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Background: Sorafenib is a standard therapy for patients with advanced hepatocellular carcinoma (HCC). However, no predictive biomarkers of sorafenib efficacy have been discovered. Herein, we investigated the impact of body composition, such as skeletal muscle and visceral fat, on the prognosis of advanced HCC patients treated with sorafenib. Methods: We enrolled 100 patients with advanced HCC treated with sorafenib. Prior to receiving sorafenib therapy, skeletal muscle index (SMI) and visceral fat area (VFA) were measured using computed tomography at the third lumbar vertebra and umbilical level, respectively. Muscle depletion was defined as an SMI value < 42 cm²/m² in men and < 38 cm²/m² in women. High VFA (H-VFA) was defined as a value ≥100 cm². In addition to SMI and VFA, we also analyzed various clinical parameters as potential prognostic factors. Results: Multivariate analysis showed that having a tumor number < 7 (hazard ratio [HR] = 0.409, p < 0.001), absence of extrahepatic spread (EHS) (HR = 0.562, p < 0.001), absence of muscle depletion (HR = 0.498, p = 0.006), and H-VFA (HR = 0.556, p = 0.031) were significant factors for long-term survival. Therefore, we evaluated the prognosis of those with no muscle depletion with H-VFA. The no muscle depletion with H-VFA group showed significantly longer survival than the other group (median survival time 15.6 vs. 11.0 months, p = 0.003). Multivariate analysis showed that having a tumor number < 7 (HR = 0.454, p = 0.001), absence of EHS (HR = 0.511, p = 0.008), and no muscle depletion with H-VFA (HR = 0.454, p = 0.002) were significant predictors of survival. Conclusions: We identified no muscle depletion with H-VFA as a novel biomarker for advanced HCC patients treated with sorafenib.

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“…It has recently been shown that the impact of sorafenib is largely confined to the patients who are HCV positive [25,26]. The present NMA cannot account for this specific aspect to be ascertained, and the investigation of this issue would require subgroup efficacy and safety data segregated for HCV positive and negative patients.…”

Section: Discussionmentioning

confidence: 95%

Efficacy and Safety of Systemic Therapies for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis of Phase III Trials

et al. 2017

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Aim/Background: After the introduction of sorafenib in the treatment of advanced hepatocellular carcinoma (HCC), different studies tried to evaluate whether other systemic therapies can improve survival. To provide a comprehensive indirect treatment comparison of efficacy and safety of novel drugs, a network meta-analysis (NMA) of phase III randomized controlled trials was performed. Methods: After pertinent literature search up to November 1, 2016, 6 studies were eligible for the analysis including 4,812 individual patients with advanced HCC: 2,454 received sorafenib, 577 received brivanib, 530 received sunitinib, 514 received linifanib, 358 received sorafenib + erlotinib and 379 received placebo. Frequentist NMA was used to compare treatments within a single analytical framework. Results: NMA showed that sorafenib alone, regardless of combination with erlotinib, and linifanib provide a significant survival advantage over placebo (p < 0.05) but without any significant difference between each other. Conversely, all regimens significantly ameliorate progression-free survival versus placebo (p < 0.05). The rank order of efficacy was: sorafenib ± erlotinib, linifanib, brivanib, sunitinib, and placebo. Sorafenib ± erlotinib was the regimen with the fewest number of adverse events that required discontinuation of treatment, whereas linifanib and brivanib resulted in the most adverse events. The risk-benefit summary identified one cluster of therapies with a similar balance between efficacy and safety which included sorafenib alone or in combination with erlotinib, having, at the same time, the highest efficacy and safety. Conclusions: Sorafenib remains the best systemic treatment for advanced HCC; linifanib also resulted in survival advantages over placebo but with a lower safety profile.

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Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies

Cited by 496 publications

References 45 publications

Excellent Response to Anti-PD-1 Therapy in a Patient with Hepatocellular Carcinoma Intolerant to Sorafenib

Excellent Response to Anti-PD-1 Therapy in a Patient with Hepatocellular Carcinoma Intolerant to Sorafenib

No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma

Efficacy and Safety of Systemic Therapies for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis of Phase III Trials

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