Atezolizumab plus bevacizumab versus sorafenib or atezolizumab alone for unresectable hepatocellular carcinoma: A systematic review

Ahmed, Faiza; Onwumeh-Okwundu, Jennifer; Yukselen, Zeynep; Coronel, Maria-Kassandra Endaya; Zaidi, Madiha; Guntipalli, Prathima; Garimella, Vamsi; Gudapati, Sravya; Mezidor, Marc Darlene; Andrews, Kim; Mouchli, Mohamad; Shahini, Endrit

doi:10.4251/wjgo.v13.i11.1813

Cited by 16 publications

(10 citation statements)

References 21 publications

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“…HCC in an advanced-stage (BCLC stage C) with vascular invasion or extrahepatic spread, ECOG PS ≤ 2, and preserved liver function should be evaluated for systemic therapy (1). The combination of atezolizumab with bevacizumab is the first-line treatment, exhibiting a breakthrough ORR of 33.2% and median PFS of 6.8 months and proving the superiority compared to sorafenib in survival benefit (22)(23)(24). According to Maesaka et al, although the median PFS was significantly longer in the atezolizumab plus bevacizumab group (8.8 months vs. 5.2 months), there were no significant differences in terms of median OS (not reached vs. 20.6 months) or ORR (43.8% vs. 52.4%) (25).…”

Section: Introductionmentioning

confidence: 99%

Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A review

Sun

Xu²,

Meng

et al. 2022

Front. Oncol.

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Lenvatinib plus transarterial chemoembolization (TACE)have become the first choice for patients with hepatocellular carcinoma (HCC) that are unsuitable for TACE. Sorafenib plus TACE therapy for patients with portal vein tumor thrombus (PVTT) achieved positive results. However, Lenvatinib plus TACE appeared to achieve a more advantageous result for these patients based on the phase 3 REFLECT trial. Both TACE and lenvatinib therapy have immune-stimulating effects, so would lenvatinib plus TACE and immune checkpoint inhibitors be an advantageous therapy for unresectable HCC (uHCC)? Thirteen articles from PubMed were explored to determine the efficacy and safety of lenvatinib plus TACE with or without PD-1 inhibitors therapy. Most of the adverse events (AEs) were manageable. Lenvatinib plus TACE therapy was superior to lenvatinib monotherapy with intermediate stage HCC especially beyond up-to-seven criterion and was superior to TACE monotherapy in patients with uHCC or sorafenib plus TACE therapy in patients with PVTT. Objective response rates (ORRs) of 53.1%–75%, median progression free survival (PFS) of 6.15–11.6 months, and median overall survival (OS) of 14.5–18.97 months were achieved in the lenvatinib plus TACE group. Levatinib plus TACE and PD-1 inhibitors achieved ORRs of 46.7% –80.6%, median PFS of 7.3–13.3 months, and median OS of 16.9–24 months. Control studies also confirmed the triple therapy was superior to lenvatinib plus TACE in patients with uHCC. Overall, the triple therapy is a promising treatment for patients with uHCC, including main PVTT and extrahepatic metastasis. Lenvatinib plus TACE therapy was also preferable for intermediate stage HCC beyond up-to-seven criterion and for patients with PVTT.

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Section: Introductionmentioning

confidence: 99%

Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A review

Sun

Xu²,

Meng

et al. 2022

Front. Oncol.

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“…There are a considerable number of studies and clinical trials on targeted drugs in HCC and CCC. (We cannot cite all of these studies; therefore, for review see: [ 18 , 23 , 24 ]). In the vast majority of cases, these studies focus on specific tumor entities, HCC or CCC.…”

Section: Introductionmentioning

confidence: 99%

Differential in vitro effects of targeted therapeutics in primary human liver cancer: importance for combined liver cancer

Malik¹,

Rajput²,

Werner

et al. 2022

BMC Cancer

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The incidence of primary liver tumors, hepatocellular carcinoma (HCC), intrahepatic cholangiocellular carcinoma (ICC), and combined HCC/ICC (cHCC/CC) is increasing. For ICC, targeted therapy exists only for a small subpopulation of patients, while for HCC, Sorafenib and Lenvatinib are in use. Diagnosis of cHCC/CC is a great challenge and its incidence is underestimated, bearing the risk of unintended non-treatment of ICC. Here, we investigated effects of targeted inhibitors on human ICC cell lines (HUH28, RBE, SSP25), in comparison to extrahepatic (E)CC lines (EGI1, CCC5, TFK1), and HCC/hepatoblastoma cell lines (HEP3B, HUH7, HEPG2). Cells were challenged with: AKT inhibitor MK-2206; multikinase inhibitors Sorafenib, Lenvatinib and Dasatinib; PI3-kinase inhibitors BKM-120, Wortmannin, LY294002, and CAL-101; and mTOR inhibitor Rapamycin. Dosage of the substances was based on the large number of published data of recent years. Proliferation was analyzed daily for four days. All cell lines were highly responsive to MK-2206. Thereby, MK-2206 reduced expression of phospho(p)-AKT in all ICC, ECC, and HCC lines, which mostly corresponded to reduction of p-mTOR, whereas p-ERK1/2 was upregulated in many cases. Lenvatinib showed inhibitory effects on the two HCC cell lines, but not on HEPG2, ICCs and ECCs. Sorafenib inhibited proliferation of all cells, except the ECC line CCC5. However, at reduced dosage, we observed increased cell numbers in some ICC experiments. Dasatinib was highly effective especially in ICC cell lines. Inhibitory effects were observed with all four PI3-kinase inhibitors. However, cell type-specific differences were also evident here. Rapamycin was most effective in the two HCC cell lines. Our studies show that the nine inhibitors differentially target ICC, ECC, and HCC/hepatoblastoma lines. Caution should be taken with Lenvatinib and Sorafenib administration in patients with cHCC/CC as the drugs may have no effects on, or might even stimulate, ICC.

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“…17 The choice of therapy is also essentially operator and institution depend- Recent studies have evaluated the efficacy and safety of new systemic antineoplastic therapies (atezolizumab/bevacizumab) compared with conventional first-line treatment with sorafenib in patients with unresectable HCC, demonstrating significantly increased OS and PFS rates. 31,32 However, to our knowledge, no studies have been conducted comparing the clinical outcomes and disease prognosis associated with the use of local ablative treatments and these newer chemotherapeutic agents in HCC.…”

Section: Discussionmentioning

confidence: 99%

Microwave ablation as a primary versus secondary treatment for hepatocellular carcinoma

Lee¹,

Makkena²,

Tantawi³

et al. 2023

dir

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T he incidence of hepatocellular carcinoma (HCC) recurrence following surgical resection and locoregional therapy (LRT) performed with curative intent is high. Three-year local progression rates after radiofrequency ablation (RFA) vary widely between institutions, ranging from 3.2% to 21.9%. [1][2][3] Recurrence rates of 50% to 70% (of which 80% to 90% are intrahepatic) have been reported five years after hepatectomy. 4 Such recurrences constitute a significant cause of late mortality.Trans-arterial therapies have traditionally been recommended in those with large tumors or multifocal disease (intermediate stage). Since some patients' treatment goals are palliative, it is common for patients to undergo more than one treatment, sometimes using combination therapies to achieve disease control. 5 The reported rates of residual disease post-trans-arte- PURPOSEThe purpose of this study was to analyze and compare the outcomes of percutaneous microwave ablation (MWA) when used as a primary vs. secondary treatment for hepatocellular carcinoma (HCC). METHODSThe clinical data of 192 patients with HCC treated with MWA between January 2012 and July 2021 were reviewed retrospectively, with 152 patients being treatment naïve (primary treatment) vs. 40 who had residual or recurrent disease following previous trans-arterial chemoembolization or trans-arterial radioembolization (secondary treatment). The primary outcomes were primary technical efficacy, 1-and 3-year local recurrence-free survival (RFS) and overall survival (OS), local recurrence rates, and adverse events. Pre-and post-intervention liver function tests were compared using a Wilcoxon signed rank test. Univariate and multivariate analyses were also performed, looking at prognostic factors associated with OS and local RFS. RESULTSThere was no significant difference in 1-year local RFS (primary 93.6% vs. secondary 93.7; P = 0.97) and 3-year local RFS (primary 80.6% vs. secondary 86.5%; P = 0.37) rates. There was no significant difference in 1-year OS (primary 82.4% vs. secondary 86.6%; P = 0.51) and 3-year OS (primary 68.3% vs. secondary 77.4%; P = 0.25) between the two groups. The local recurrence rate (primary 9.8% vs. secondary 14.6%; P = 0.37), primary technical efficacy (primary 96.2% vs. secondary 95%; P = 0.73), and adverse events (primary 8.0% vs. secondary 11.6%; P = 0.45) were also similar between the two groups. CONCLUSIONMicrowave ablation is safe and effective as a secondary treatment for patients with HCC in a clinical salvage scenario and should be utilized more frequently.

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Atezolizumab plus bevacizumab versus sorafenib or atezolizumab alone for unresectable hepatocellular carcinoma: A systematic review

Cited by 16 publications

References 21 publications

Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A review

Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A review

Differential in vitro effects of targeted therapeutics in primary human liver cancer: importance for combined liver cancer

Microwave ablation as a primary versus secondary treatment for hepatocellular carcinoma

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