Atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma

Xu, Yang; Wang, Dongxu; Lin, Jianzhen; Yang, Xiaobo; Zhao, Haitao

doi:10.1016/s1470-2045(20)30430-7

Cited by 27 publications

(20 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A phase III clinical trial (NCT03434379) of bevacizumab with PD-L1 inhibitor atezolizumab showed a superior outcome in overall and progression-free survival than sorafenib in advanced HCC cases ( Finn et al, 2020 ). Due to this encouraging result, FDA approved the combined use of bevacizumab and atezolizumab as the first-line treatment for unresectable HCC patients ( Yang et al, 2020 ). A recent report on targeting aberrant mRNA modification in leukemia has highlighted another potential therapeutic approach to suppress fat mass and obesity-associated protein (FTO), an RNA N6-methyladenosine (m6A) demethylase ( Su et al, 2020 ).…”

Section: Development Of Csc-targeted Immunotherapymentioning

confidence: 99%

Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers

Lei

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Cancer stem cells (CSCs) are subpopulations of undifferentiated cancer cells within the tumor bulk that are responsible for tumor initiation, recurrence and therapeutic resistance. The enhanced ability of CSCs to give rise to new tumors suggests potential roles of these cells in the evasion of immune surveillance. A growing body of evidence has described the interplay between CSCs and immune cells within the tumor microenvironment (TME). Recent data have shown the pivotal role of some major immune cells in driving the expansion of CSCs, which concurrently elicit evasion of the detection and destruction of various immune cells through a number of distinct mechanisms. Here, we will discuss the role of immune cells in driving the stemness of cancer cells and provide evidence of how CSCs evade immune surveillance by exerting their effects on tumor-associated macrophages (TAMs), dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), T-regulatory (Treg) cells, natural killer (NK) cells, and tumor-infiltrating lymphocytes (TILs). The knowledge gained from the interaction between CSCs and various immune cells will provide insight into the mechanisms by which tumors evade immune surveillance. In conclusion, CSC-targeted immunotherapy emerges as a novel immunotherapy strategy against cancer by disrupting the interaction between immune cells and CSCs in the TME.

show abstract

Section: Development Of Csc-targeted Immunotherapymentioning

confidence: 99%

Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers

Lei

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…However, due to the high cost of research and development, the legislation preventing Medicare from being able to negotiate the drug prices, and a lack of value-based pricing system, like many new cancer drugs, the atezo-bev combination is expensive. Therefore [16], it is pressing to define its value for policymakers, payers, patients, and clinicians, particularly from the global perspective given the high incidence of HCC in economically disadvantaged regions worldwide [17,18].…”

Section: Introductionmentioning

confidence: 99%

First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

Chiang

Chan

Lee

et al. 2021

Cancers

View full text Add to dashboard Cite

Background: The IMbrave 150 trial revealed that atezolizumab plus bevacizumab (atezo–bev) improves survival in patients with unresectable hepatocellular carcinoma (HCC) (1 year survival rate: 67.2% vs. 54.6%). We assessed the cost-effectiveness of atezo–bev vs. sorafenib as first-line therapy in patients with unresectable HCC from the US payer perspective. Methods: Using data from the IMbrave 150, we developed a Markov model to compare the lifetime cost and efficacy of atezo–bev as first-line systemic therapy in HCC with those of sorafenib. The main outcomes were life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results: Atezo–bev demonstrated a gain of 0.44 QALYs, with an additional cost of USD 79,074. The ICER of atezo–bev was USD 179,729 per QALY when compared with sorafenib. The model was most sensitive to the overall survival hazard ratio and body weight. If we assumed that all patients at the end of the IMbrave 150 trial were cured of HCC, atezo–bev was cost-effective (ICER USD 53,854 per QALY). However, if all patients followed the Surveillance, Epidemiology, and End Results data, the ICER of atezo–bev was USD 385,857 per QALY. Reducing the price of atezo–bev by 20% and 29% would satisfy the USD 150,000/QALY and 100,000/QALY willingness-to-pay threshold. Moreover, capping the duration of therapy to ≤12 months or reducing the dosage of bev to ≤10 mg/kg would render atezo–bev cost-effective. Conclusions: The long-term effectiveness of atezo–bev is a critical but uncertain determinant of its cost-effectiveness. Price reduction would favorably influence cost-effectiveness, even if long-term clinical outcomes were modest. Further studies to optimize the duration and dosage of therapy are warranted.

show abstract

“…Recently, a global, open-label, phase 3 trial has shown that the VEGF blocking mAb bevacizumab combined with anti-PD-L1 improved overall and progression-free survival outcomes compared to standard-of-care sorafenib in unresectable hepatocellular carcinoma (38,39). Clinical studies are also investigating anti-VEGF strategies in combination with other immune therapies including CTLA-4 blockade or CD40 agonism (40)(41)(42).…”

Section: Selective Inhibition Of Vegf Activation Of Vegfr2 With Mcr84 Increases the Expression Of Adhesion Molecules While Decreasing Expmentioning

confidence: 99%

VEGFR2 activity on myeloid cells mediates immune suppression in the tumor microenvironment

Zhang¹,

Huang²,

Coleman³

et al. 2021

JCI Insight

View full text Add to dashboard Cite

Angiogenesis, a hallmark of cancer, is induced by vascular endothelial growth factor-A (VEGF). As a result, anti-VEGF therapy is commonly employed for cancer treatment. Recent studies have found that VEGF expression is also associated with immune suppression in cancer patients. This connection has been investigated in preclinical and clinical studies by evaluating the therapeutic effect of combining anti-angiogenic reagents with immune therapy. However, the mechanisms of how anti-VEGF strategies enhance immune therapy are not fully understood. We and others have shown selective elevation of VEGFR2 expression on tumor-associated myeloid cells in tumorbearing animals. Here we investigated the function of VEGFR2 + myeloid cells in regulating tumor immunity and found VEGF induces an immunosuppressive phenotype in VEGFR2 + myeloid cells including directly upregulating the expression of programmed cell death 1-ligand 1 (PD-L1).Moreover, we found that VEGF blockade inhibits the immunosuppressive phenotype of VEGFR2 + myeloid cells, increases T cell activation and enhances the efficacy of immune checkpoint blockade.This study highlights the function of VEGFR2 on myeloid cells and provides mechanistic insight on how VEGF inhibition potentiates immune checkpoint blockade.

show abstract

Atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma

Cited by 27 publications

References 4 publications

Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers

Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers

First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

VEGFR2 activity on myeloid cells mediates immune suppression in the tumor microenvironment

Contact Info

Product

Resources

About