Comparative efficacy of novel combination strategies for unresectable hepatocellular carcinoma: A network metanalysis of phase III trials

Fulgenzi, Claudia Angela Maria; D’Alessio, Antonio; Airoldi, Chiara; Scotti, Lorenza; Demirtaş, Coşkun Özer; Giorgi, Ugo De; Cortellini, Alessio; Pinato, David J.

doi:10.1016/j.ejca.2022.06.058

Cited by 33 publications

(22 citation statements)

References 36 publications

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“…In this study, we also uniformly selected sorafenib as a control. However, our findings differed slightly from those of published research ( 21 ). Network meta-analysis results revealed that sintilimab plus a bevacizumab biosimilar showed the best effectiveness in prolonging OS, followed by camrelizumab plus rivoceranib and atezolizumab plus bevacizumab.…”

Section: Discussioncontrasting

confidence: 99%

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Immunotherapy or targeted therapy as the first-line strategies for unresectable hepatocellular carcinoma: A network meta-analysis and cost-effectiveness analysis

2023

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IntroductionThe existence of many phase III randomized controlled trials (RCTs) of first-line treatment for unresectable hepatocellular carcinoma (HCC) puzzle doctors and patients in choosing the most effective treatment strategies. We aimed to assess the efficacy, safety, and cost-effectiveness of immunotherapy or targeted therapy as the first-line strategy for unresectable HCC.MethodsThe included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and Web of Science databases, in which immunotherapy or targeted therapy was regarded as the first-line treatment for unresectable HCC, published in English between January 1, 2010, and September 20, 2022. We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) from the Chinese payer’s perspective. Overall survival (OS), progression-free survival (PFS), the ranks of different treatments using P-score, and adverse events (AEs) were evaluated by NMA. Total costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated from 15-year Markov models developed by CEA.ResultsWe identified 2,825 records, including 11,796 patients, from 15 RCTs. The NMA revealed that sintilimab plus a bevacizumab biosimilar (HR, 0.57; 95% CI, 0.43 to 0.75; P = 0.96) and camrelizumab plus rivoceranib (HR, 0.56; 95% CI, 0.41 to 0.66; P = 0.94) could lead to great improvements in OS and PFS compared with sorafenib-related survival. The CEA indicated that tislelizumab increased by 0.220 QALYs (0.312 LYs) and decreased by $1,938 compared with sorafenib, which yielded ICERs of -$8,809/QALY (-$2,612/LY). Sensitivity analysis showed that the model was stable.ConclusionSintilimab plus a bevacizumab biosimilar and camrelizumab plus rivoceranib significantly prolonged OS and PFS, respectively. Further considering the pharmacoeconomics factors, tislelizumab is the most cost-effective first-line treatment strategy for unresectable HCC in China.

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Section: Discussioncontrasting

confidence: 99%

“…found that sintilimab plus a bevacizumab biosimilar was the most effective treatment ( 20 ). In addition, another paper demonstrated that atezolizumab plus bevacizumab and sintilimab plus a bevacizumab biosimilar were comparable in efficacy ( 21 ). These studies have also become data references for clinical medication.…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy or targeted therapy as the first-line strategies for unresectable hepatocellular carcinoma: A network meta-analysis and cost-effectiveness analysis

2023

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“…376,377 Combinational treatments with PD-L1/PD-1 blockade, CTLA-4 inhibitors, and small molecule IDO inhibitors have also resulted in strongly enhanced tumor suppression in multiple tumor models (including osteosarcoma models) because they expand infiltrating T lymphocytes and decrease Treg and MDSC numbers. [378][379][380] For The horizons for osteosarcoma treatment H Tian et al…”

Section: Immune Checkpoint Blockade-based Immunotherapy For Osteosarcomamentioning

confidence: 99%

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

Tian

Cao

et al. 2023

Bone Res

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Osteosarcoma, with poor survival after metastasis, is considered the most common primary bone cancer in adolescents. Notwithstanding the efforts of researchers, its five-year survival rate has only shown limited improvement, suggesting that existing therapeutic strategies are insufficient to meet clinical needs. Notably, immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis. Therefore, managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease. Additionally, given the advances in nanomedicine, there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics. Here, we review the classification, characteristics, and functions of the key components of the immune microenvironment in osteosarcoma. This review also emphasizes the application, progress, and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment. Furthermore, we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.

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“…In recent decades, immunotherapy has revolutionized HCC treatment. Data from the IMbrave150 trial , and other phase 3 trials , suggest that combinatorial treatment strategies that incorporate regimens based on immune checkpoint inhibitors are promising treatment approaches for patients with HCC. However, tumor cells are capable of developing resistance and evading immune eradication, limiting the benefits of immune checkpoint blockade therapy, with <20–40% of patients experiencing positive outcomes .…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Activation of Immunogenic Cell Death and cGAS-STING Pathway by Liver- and Mitochondria-Targeted Gold(I) Complexes for Chemoimmunotherapy of Hepatocellular Carcinoma

Li,

Wen,

et al. 2024

J. Med. Chem.

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Induction of immunogenic cell death (ICD) and activation of the cyclic GMP-AMP synthase stimulator of interferon gene (cGAS-STING) pathway are two potent anticancer immunotherapeutic strategies in hepatocellular carcinoma (HCC). Herein, 12 liverand mitochondria-targeting gold(I) complexes (9a−9l) were designed and synthesized. The superior complex 9b produced a considerable amount of reactive oxygen species (ROS) and facilitated DNA excretion, the ROS-induced ICD and DNA activated the cGAS-STING pathway, both of which evoked an intense anticancer immune response in vitro and in vivo. Importantly, 9b strongly inhibited tumor growth in a patientderived xenograft model of HCC. Overall, we present the first case of simultaneous ICD induction and cGAS-STING pathway activation within the same gold-based small molecule, which may provide an innovative strategy for designing chemoimmunotherapies for HCC.

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Comparative efficacy of novel combination strategies for unresectable hepatocellular carcinoma: A network metanalysis of phase III trials

Cited by 33 publications

References 36 publications

Immunotherapy or targeted therapy as the first-line strategies for unresectable hepatocellular carcinoma: A network meta-analysis and cost-effectiveness analysis

Immunotherapy or targeted therapy as the first-line strategies for unresectable hepatocellular carcinoma: A network meta-analysis and cost-effectiveness analysis

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

Simultaneous Activation of Immunogenic Cell Death and cGAS-STING Pathway by Liver- and Mitochondria-Targeted Gold(I) Complexes for Chemoimmunotherapy of Hepatocellular Carcinoma

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