Sorafenib as first-line therapy in patients with advanced Child-Pugh B hepatocellular carcinoma—a meta-analysis

McNamara, Mairéad G.; Slagter, Astrid E.; Nuttall, Christina; Frizziero, Melissa; Pihlak, Rille; Lamarca, Ángela; Tariq, Noor; Valle, Juan W; Hubner, Richard A; Knox, Jennifer J.; Amir, Eitan

doi:10.1016/j.ejca.2018.09.031

Cited by 77 publications

(70 citation statements)

References 47 publications

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“…Finally, since the data were collected retrospectively from electronic medical records, only adverse events resulting in drug discontinuation or dose delay could be identified in detail. However, considering that nivolumab was well-tolerated, with the exception of rarely occurring severe immune-mediated adverse events seen in previous studies [ 6 , 10 , 11 , 12 , 18 , 21 ], we believe that the information on adverse events of our study contains clinically meaningful information despite the lack of detailed adverse event information.…”

Section: Discussionmentioning

confidence: 83%

“…The most widely reported systemic therapy in this population is sorafenib. A meta-analysis of thirty studies demonstrated that Child–Pugh B liver function is associated with worse OS compared to Child–Pugh A liver function despite similar response rate, safety, and tolerability [ 21 ]. Several previous studies have evaluated the efficacy and safety of nivolumab in Child–Pugh class B patients.…”

Section: Discussionmentioning

confidence: 99%

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Effectiveness and Safety of Nivolumab in Child–Pugh B Patients with Hepatocellular Carcinoma: A Real-World Cohort Study

Choi

Lee

Shim

et al. 2020

Cancers

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Nivolumab has shown durable response and safety in patients with hepatocellular carcinoma (HCC) in previous trials. However, real-world data of nivolumab in HCC patients, especially those with Child–Pugh class B, are limited. To investigate the effectiveness and safety of nivolumab in a real-world cohort of patients with advanced HCC, we retrospectively evaluated 203 patients with HCC who were treated with nivolumab between July 2017 and February 2019. Of 203 patients, 132 patients were classified as Child–Pugh class A and 71 patients were Child–Pugh class B. Objective response rate was lower in patients with Child–Pugh class B than A (2.8% vs. 15.9%; p = 0.010). Child–Pugh class B was an independent negative predictor for objective response. Median overall survival was shorter in Child–Pugh B patients (11.3 vs. 42.9 weeks; adjusted hazard ratio [AHR], 2.10; p < 0.001). In Child–Pugh B patients, overall survival of patients with Child–Pugh score of 8 or 9 was worse than patients with Child–Pugh score of 7 (7.4 vs. 15.3 weeks; AHR, 1.93; p < 0.020). In conclusion, considering the unsatisfactory response in Child–Pugh B patients, nivolumab may not be used in unselected Child–Pugh B patients. Further studies are needed in this patient population.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of Nivolumab in Child–Pugh B Patients with Hepatocellular Carcinoma: A Real-World Cohort Study

Choi

Lee

Shim

et al. 2020

Cancers

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“…However, a sizable number of patients with advanced HCC in clinical practice have Child Pugh B cirrhosis at time of presentation, highlighting a need for data in extended patient populations. Unfortunately, a phase III trial (BOOST, NCT01405573) investigating sorafenib in patients with Child‐Pugh B was terminated due to lack of enrollment, so there continues to be a lack of phase III data in these patients . However, the GIDEON study, a global, prospective, non‐interventional study designed to evaluate the safety of sorafenib in patients in real‐life practice, included 666 (21%) patients with Child‐Pugh B cirrhosis and provides some insight into this population .…”

Section: First Line Therapiesmentioning

confidence: 99%

“…Unfortunately, a phase III trial (BOOST, NCT01405573) investigating sorafenib in patients with Child-Pugh B was terminated due to lack of enrollment, so there continues to be a lack of phase III data in these patients. 9 However, the GIDEON study, a global, prospective, noninterventional study designed to evaluate the safety of sorafenib in patients in real-life practice, included 666 (21%) patients with Child-Pugh B cirrhosis and provides some insight into this population. 10 As expected, the median survival was longer in Child-Pugh A patients compared with Child-Pugh B patients (13.6 vs 5.2 months).…”

Section: Sorafenibmentioning

confidence: 99%

Review article: new therapeutic interventions for advanced hepatocellular carcinoma

Bangaru

Marrero

Singal

2019

Aliment Pharmacol Ther

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Summary Background Advanced hepatocellular carcinoma (HCC) portends a poor prognosis; however recent advances in first‐line and second‐line treatment options should yield significant improvements in survival. Aim To summarize the evolving landscape of treatment options for patients with advanced HCC. Methods We reviewed published clinical trials conducted in patients with advanced HCC published in PubMed or presented at national conferences. Results Sorafenib was approved for treatment of unresectable HCC in 2007 and remained the only therapy with proven survival benefit in advanced HCC for several years. Lenvatinib, another tyrosine‐kinase inhibitor, was recently shown to have non‐inferior survival vs sorafenib and is another first‐line treatment option. The tyrosine‐kinase inhibitors, regorafenib and cabozantinib, were shown to significantly improve survival in the second‐line setting after sorafenib failure. Ramucirumab, a VEGF inhibitor, can also improve survival in the second‐line setting among patients with AFP ≥ 400 ng/dL. Phase II data highlight potential durable objective responses with immune checkpoint inhibitors, prompting conditional FDA approval of nivolumab and pembrolizumab in the second‐line setting; however, recent phase III data have failed to demonstrate improved survival compared to other treatment options. Ongoing trials are evaluating combination immune checkpoint inhibitor and immune checkpoint inhibitors with tyrosine‐kinase inhibitors or VEGF inhibitors in hopes of further increasing objective responses and overall survival in this patient population. Conclusion There are several first‐line and second‐line therapeutic options available for patients with advanced HCC. Further studies are needed to determine how best to select between and sequence the growing number of therapeutic options.

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“…( 7‐9 ) Additionally, it is often compromised by systemic side effects, such as hand–foot skin reaction, diarrhea, nausea/vomiting, and weight loss in 81.9% of patients, requiring dose reduction or interruption of therapy. ( 10 ) Effective titration of chemotherapy dosage while limiting side effects is difficult given dependence on drug‐metabolizing enzymes in the liver. ( 9 ) There is, therefore, a dire need to develop therapies for advanced HCC that bypass hepatic metabolism and deliver therapy directly into the malignant hepatocytes.…”

mentioning

confidence: 99%

Lipoprotein‐Like Nanoparticle Carrying Small Interfering RNA Against Spalt‐Like Transcription Factor 4 Effectively Targets Hepatocellular Carcinoma Cells and Decreases Tumor Burden

et al. 2020

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Patients with advanced hepatocellular carcinoma (HCC) are often unable to tolerate chemotherapy due to liver dysfunction in the setting of cirrhosis. We investigate high-density lipoprotein (HDL)-mimicking peptide phospholipid scaffold (HPPS), which are nanoparticles that capitalize on normal lipoprotein metabolism and transport, as a solution for directed delivery of small interfering RNA (siRNA) cargo into HCC cells. Spalt-like transcription factor 4 (SALL4), a fetal oncoprotein expressed in aggressive HCCs, is specifically targeted as a case study to evaluate the efficacy of HPPS carrying siRNA cargo. HPPS containing different formulations of siRNA therapy against SALL4 were generated specifically for HCC cells. These were investigated both in vitro and in vivo using fluorescence imaging. HPPS-SALL4 effectively bound to scavenger receptor, class B type 1 (SR-BI) and delivered the siRNA cargo into HCC cells, as seen in vitro. HPPS-SALL4 effectively inhibited HCC tumor growth (P < 0.05) and induced a 3-fold increase in apoptosis of the cancer cells in vivo compared to HPPS-scramble. Additionally, there was no immunogenicity associated with HPPS-SALL4 as measured by cytokine production. Conclusion: We have developed unique HDLlike nanoparticles that directly deliver RNA interference (RNAi) therapy against SALL4 into the cytosol of HCC cells, effectively inhibiting HCC tumor growth without any systemic immunogenicity. This therapeutic modality avoids the need for hepatic metabolism in this cancer, which develops in the setting of cirrhosis and liver dysfunction. These natural lipoprotein-like nanoparticles with RNAi therapy are a promising therapeutic strategy for HCC. (Hepatology Communications 2020;4:769-782).

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Sorafenib as first-line therapy in patients with advanced Child-Pugh B hepatocellular carcinoma—a meta-analysis

Cited by 77 publications

References 47 publications

Effectiveness and Safety of Nivolumab in Child–Pugh B Patients with Hepatocellular Carcinoma: A Real-World Cohort Study

Effectiveness and Safety of Nivolumab in Child–Pugh B Patients with Hepatocellular Carcinoma: A Real-World Cohort Study

Review article: new therapeutic interventions for advanced hepatocellular carcinoma

Lipoprotein‐Like Nanoparticle Carrying Small Interfering RNA Against Spalt‐Like Transcription Factor 4 Effectively Targets Hepatocellular Carcinoma Cells and Decreases Tumor Burden

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