Atezolizumab Plus Bevacizumab in Patients with Advanced and Progressing Hepatocellular Carcinoma: Retrospective Multicenter Experience

Sinner, Friedrich; Pinter, Matthias; Scheiner, Bernhard; Ettrich, Thomas Jens; Sturm, Niklas; Gonzalez‐Carmona, Maria A.; Waidmann, Oliver; Finkelmeier, Fabian; Himmelsbach, Vera; Toni, Enrico N. De; Khaled, Najib Ben; Mohr, Raphael; Fründt, Thorben W.; Kütting, Fabian; Boemmel, Florian van; Lieb, Sabine; Krug, Sebastian; Bettinger, Dominik; Schultheiß, Michael; Jochheim, Leonie; Best, Jan; Müller, Christian; Keitel, Verena; Venerito, Marino

doi:10.3390/cancers14235966

Cited by 14 publications

(22 citation statements)

References 23 publications

(28 reference statements)

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“…Atezo-Bev exerts immune-modulatory effects by blocking PD-1/PD-L1 pathways and inhibiting neovascularization by suppressing the action of VEGF. Several real-world studies reported after the IMbrave 150 trial have verified the robust efficacy and favorable safety profile of using these therapies in combination for advanced HCC 9–12 . However, using Atezo-Bev is not without risks, as both individual drugs have specific considerations that can impact survival regardless of an antitumor response.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Survival in Patients With Hepatocellular Cancer Receiving Atezolizumab and Bevacizumab

Ledenko,

Mercado,

Patel

2023

American Journal of Clinical Oncology

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Objectives: In randomized clinical trials in patients with hepatocellular cancer (HCC), combination therapy with atezolizumab and bevacizumab (Atezo-Bev) prolonged survival, and these treatments have become the standard first-line therapy for advanced HCC. However, clinical trials may not reflect real-life clinical practice due to treatment selection criteria. Thus, our aim was to understand predictors of HCC outcomes with these treatments in a real-world, multicenter setting. Methods: A retrospective review of all patients 18 years of age or older treated for advanced primary liver cancer between February 2020 and August 2022 was conducted to assess the relationship between overall survival and clinical and biochemical variables before or during treatment. Univariate and multivariate Cox regression survival analyses were performed to identify predictors of survival following treatment. Results: One hundred and eleven eligible patients with unresectable HCC received Atezo-Bev over a consecutive 30-month period. Cox regression identified several significant (P<0.05) predictors of survival, including pretreatment albumin (hazard ratios [HR]: 0.2; CI: 0.1-0.4), total bilirubin (HR: 1.3; CI: 1.2-1.5), and international normalized ratio (HR: 5.6; CI: 2.5-12.5). In multivariate analyses, these were significantly associated as predictors of mortality, and patients with pretreatment albumin <3.5 mg/dL had significantly lower survival than those ≥3.5 (153 vs. 522 d, P<0.0001). Conclusions: Pretreatment hypoalbuminemia, high bilirubin, and biochemical tests indicative of hepatic or renal dysfunction can independently predict short-term mortality in advanced HCC patients receiving Atezo-Bev.

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Section: Discussionmentioning

confidence: 99%

Predictors of Survival in Patients With Hepatocellular Cancer Receiving Atezolizumab and Bevacizumab

Ledenko,

Mercado,

Patel

2023

American Journal of Clinical Oncology

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“…The FDA approved the combinational ICI and additional combinations of durvalumab and tremelimumab for the PDCD1 in light of these positive results [37]. Atemalizumab and bevacizumab were licensed by the FDA for use in immunotherapy for the first HCC combination on a worldwide scale [38]. These findings have led to the present clinical trials of a number of ICI combinations on patients receiving systemic immune treatment.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Somatic Mutations in the TCGA-LIHC Whole Exome Sequence to Identify the Neoantigen for Immunotherapy in Hepatocellular Carcinoma

Pulakuntla,

Syed,

Reddy

2023

CIMB

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There are numerous clinically proven methods for treating cancer worldwide. Immunotherapy has been used to treat cancer with significant success in the current studies. The purpose of this work is to identify somatically altered target gene neoantigens and investigate liver cancer-related immune cell interaction and functional changes for potential immunotherapy in future clinical trials. Clinical patient data from the Cancer Genome Atlas (TCGA) database were used in this investigation. The R maf utility package was used to perform somatic analysis. The 17-mer peptide neoantigens were extracted using an in-house Python software called Peptide.py. Additionally, the epitope analysis was conducted using NetMHCpan4.1 program. Neopeptide immunogenicity was assessed using DeepCNN-Ineo, and tumor immune interaction, association with immune cells, correlation, and survival analysis were assessed using the TIMER web server. Based on somatic mutation analysis, we have identified the top 10 driver genes (TP53, TNN, CTNNB1, MUC16, ALB, PCLO, MUC4, ABCA13, APOB, and RYR2). From the superfamily of 20 HLA (Human leukocyte antigens) allele epitopes, we discovered 5653 neopeptides. Based on T cell receptor face hydrophobic analysis, these neopeptides were subjected to immunogenicity investigation. A mutation linked to tumor growth may have an impact on immune cells. According to this study’s correlation and survival analysis, all driver genes may function as immune targets for liver cancer. These genes are recognized to be immune targets. In the future, immune checkpoint inhibitors may be developed to prolong patient survival times and prevent hepatocellular carcinoma (HCC) through immunotherapy.

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“…Extrapolating from the IMbrave150 study in the first-line setting, it is the opinion of the Expert Panel that atezo 1 bev may be considered as second-line therapy in select patients who have progressed on or are intolerant of first-line sorafenib or lenvatinib and do not have contraindications to this combination. 49 In addition, a phase III RCT of ICI pembrolizumab as secondline therapy following sorafenib was included in the systematic review. The response rate of 18% in the pembrolizumab group was similar to that observed in previous smaller studies, however, there was no difference in PFS or OS compared to placebo.…”

Section: Apatinib Versus Placebo (Ahelp)mentioning

confidence: 99%

“…Extrapolating from the IMbrave150 study in the first-line setting, it is the opinion of the Expert Panel that atezo + bev may be considered as second-line therapy in select patients who have progressed on or are intolerant of first-line sorafenib or lenvatinib and do not have contraindications to this combination. 49…”

Section: Recommendationsmentioning

confidence: 99%

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update

Gordan,

Kennedy,

Abou-Alfa

et al. 2024

JCO

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PURPOSE To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC). METHODS ASCO convened an Expert Panel to update the 2020 guideline on systemic therapy for HCC. The panel updated the systematic review to include randomized controlled trials (RCTs) published through October 2023 and updated recommendations. RESULTS Ten new RCTs met the inclusion criteria and were added to the evidence base. RECOMMENDATIONS Atezolizumab + bevacizumab (atezo + bev) or durvalumab + tremelimumab (durva + treme) may be offered first-line for patients with advanced HCC, Child-Pugh class A liver disease, and Eastern Cooperative Oncology Group performance status 0-1. Where there are contraindications to these therapies, sorafenib, lenvatinib, or durvalumab may be offered first-line. Following first-line treatment with atezo + bev, second-line therapy with a tyrosine kinase inhibitor (TKI), ramucirumab (for patients with alpha-fetoprotein [AFP] ≥400 ng/mL), durva + treme, or nivolumab + ipilimumab (nivo + ipi) may be recommended for appropriate candidates. Following first-line therapy with durva + treme, second-line therapy with a TKI is recommended. Following first-line treatment with sorafenib or lenvatinib, second-line therapy options include cabozantinib, regorafenib for patients who previously tolerated sorafenib, ramucirumab (AFP ≥400 ng/mL), nivo + ipi, or durvalumab; atezo + bev or durva + treme may be considered for patients who did not have access to these therapies in the first-line setting, and do not have contraindications. Pembrolizumab or nivolumab are also options for appropriate patients following sorafenib or lenvatinib. Third-line therapy may be considered in Child-Pugh class A patients with good PS, using one of the agents listed previously that has a nonidentical mechanism of action with previously received therapy. A cautious approach to systemic therapy is recommended for patients with Child-Pugh class B advanced HCC. Further guidance on choosing between options is included within the guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

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Atezolizumab Plus Bevacizumab in Patients with Advanced and Progressing Hepatocellular Carcinoma: Retrospective Multicenter Experience

Cited by 14 publications

References 23 publications

Predictors of Survival in Patients With Hepatocellular Cancer Receiving Atezolizumab and Bevacizumab

Predictors of Survival in Patients With Hepatocellular Cancer Receiving Atezolizumab and Bevacizumab

Analysis of Somatic Mutations in the TCGA-LIHC Whole Exome Sequence to Identify the Neoantigen for Immunotherapy in Hepatocellular Carcinoma

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update

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