AGA Clinical Practice Guideline on Systemic Therapy for Hepatocellular Carcinoma

Su, Grace L.; Altayar, Osama; O’Shea, Robert; Shah, Raj; Estfan, Bassam; Wenzell, Candice M.; Sultan, Shahnaz; Falck‐Ytter, Yngve

doi:10.1053/j.gastro.2021.12.276

Cited by 128 publications

(98 citation statements)

References 35 publications

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“…Nonetheless, the prognosis of patients receiving TACE/HAIC remains poor with the median progression-free survival (PFS) of 2.8–9.6 months and most of the patients will get resistant after repeated TACE ( 9 , 11 ). For advanced uHCC patients including those with extrahepatic metastasis, systemic therapy is the preferred strategy ( 12 , 13 ). With the advent of the novel tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), sorafenib is not the only option for advanced HCC ( 14 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review

Xin

Fang

et al. 2022

Front. Immunol.

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Background and AimsRegardless of great progress in early detection of hepatocellular carcinoma (HCC), unresectable HCC (uHCC) still accounts for the majority of newly diagnosed HCC with poor prognosis. With the promising results of a double combination of transarterial chemo(embolization) and tyrosine kinase inhibitors (TKIs), and TKIs and immune checkpoint inhibitors (ICIs), a more aggressive strategy, a triple combination of transarterial chemo(embolization), TKIs, and ICIs has been tried in the recent years. Hence, we aimed to conduct a systematic review to verify the safety and efficacy of the triple therapy for uHCC.MethodsPubMed, MedLine, Embase, the Cochrane Library, and Web of Knowledge were used to screen the eligible studies evaluating the clinical efficacy and safety of triple therapy for patients with uHCC up to April 25th 2022, as well as Chinese databases. The endpoints were the complete response (CR), objective response rate (ORR), disease control rate (DCR), conversion rate, progression-free survival (PFS) rate, overall survival (OS) rate, and the incidence of adverse events (AEs).ResultsA total of 15 studies were eligible with 741 patients receiving transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with TKIs and ICIs. The pooled rate and 95% confidence interval (CI) for CR, ORR, and DCR were 0.124 (0.069–0.190), 0.606 (0.528–0.682), and 0.885 (0.835–0.927). The pooled rates for PFS at 0.5 years and 1 year were 0.781 (0.688–0.862) and 0.387 (0.293–0.486), respectively. The pooled rates for OS at 1, 2, and 3 years were 0.690 (0.585–0.786), 0.212 (0.117–0.324), and 0.056 (0.028–0.091), respectively. In addition, the pooled rate and 95%CI for the conversion surgery was 0.359 (0.153–0.595). The subgroup analysis of control studies showed that triple therapy was superior to TACE+TKIs, TKIs+ICIs, and TKIs in CR, ORR, and DCR, conversion rate; PFS; and OS. No fatal AEs were reported, and the top three most common AEs were elevated ALT, elevated AST, and hypertension, as well as severe AEs (grading ≥3).ConclusionWith the current data, we concluded that the triple therapy of TACE/HAIC, TKIs, and ICIs would provide a clinical benefit for uHCC both in short- and long-term outcomes without increasing severe AEs, but the conclusion needs further validation.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO/, Review registry: CRD42022321970.

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Section: Introductionmentioning

confidence: 99%

The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review

Xin

Fang

et al. 2022

Front. Immunol.

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“…During the era of HCC, systemic therapy has moved to a significant position. According to the results of a phase 3 trial (IMbrave 150) [ 3 ], the combination of programmed cell death-ligand 1 (PD-L1) (atezolizumab) and VEGF (bevacizumab) pathway inhibition is believed to be the most effective molecular targeted therapy for advanced HCC and is recommended as the first-line in many countries [ 4 , 5 ]. Previous reports about other molecular targeted agents for HCC, including sorafenib and lenvatinib [ 6 , 7 ], showed that the patients with sarcopenia had poor outcomes.…”

Section: Introductionmentioning

confidence: 99%

Clinical Usefulness of Monitoring Muscle Volume during Atezolizumab Plus Bevacizumab Therapy in Patients with Unresectable Hepatocellular Carcinoma

Matsumoto

Tsuchiya

Nakanishi

et al. 2022

Cancers

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Background: Sarcopenia is associated with overall survival in patients with hepatocellular carcinoma (HCC). However, it is not known whether muscle volume is associated with clinical outcomes during combination therapy with immune checkpoint inhibitors. We investigated the relationship between changes in muscle volume and treatment outcomes in patients treated with atezolizumab plus bevacizumab. Methods: Thirty-two patients with HCC who received atezolizumab plus bevacizumab as the first-line treatment between October 2020 and February 2022 were included. Skeletal muscle mass index (SMI) was calculated from the skeletal muscle area at the L3 level of the lumbar vertebrae. We compared pretreatment SMI and SMI at 6–14 weeks after administration. Results: Of the 32 patients, 18 had a decreased SMI, while 14 did not. Progression-free survival (PFS) was significantly longer in patients without SMI decrease than in patients with SMI decrease (8.5 vs. 5.8 months, p = 0.011). There were no significant differences in treatment-related adverse events between the patients with and without SMI. Presarcopenia at baseline was not significantly associated with PFS. Conclusions: Decreased SMI was significantly associated with PFS. Monitoring muscle volume during atezolizumab plus bevacizumab therapy is useful in clinical practice.

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“…In fact, it is the strain present in the only approved probiotic drug, to date, for the treatment of IBS (Alflorex ® ). However, the results are conflicting, and the American Gastroenterology Association (AGA) considers that there is a “very low quality of evidence” to recommend its use [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Commercial Probiotics on Colonic Sensitivity after Acute Mucosal Irritation

Gómez

Antón

López-Tofiño

et al. 2022

IJERPH

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Gastrointestinal pathologies associated with abdominal pain, such as irritable bowel syndrome or inflammatory bowel disease, lack sufficiently effective treatments. In our study we have used a rat model of visceral pain (72 animals; n = 8–13 per experimental group) to analyze the consequences of intracolonic administration of the irritant acetic acid on visceral sensitivity, histology of the colonic wall, and inflammatory response. Moreover, we have studied the possible beneficial effects of a pretreatment with a commercial probiotic (Actimel®). Contrary to expectations, acetic acid application (7 cm proximal to the anus) decreased the nociceptive response to intracolonic mechanical stimulation, with a slight increase in the histological damage of colonic mucosa. The intensity of these changes depended on the concentration (4% or 0.6%) and the time of application (30 or 60 min). Pretreatment with probiotics (by daily gavage, for 1 week) normalized the values obtained in the visceral sensitivity test but revealed an increase in the number of macrophages. These results suggest a possible activation of inhibitory mechanisms early after colonic irritation, not previously described (which need further experimental confirmation), and the ability of probiotics to normalize the effects of acetic acid. In addition, pretreatment with probiotics has a direct effect on immune functions, stimulating macrophagic activity.

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AGA Clinical Practice Guideline on Systemic Therapy for Hepatocellular Carcinoma

Cited by 128 publications

References 35 publications

The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review

The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review

Clinical Usefulness of Monitoring Muscle Volume during Atezolizumab Plus Bevacizumab Therapy in Patients with Unresectable Hepatocellular Carcinoma

Effects of Commercial Probiotics on Colonic Sensitivity after Acute Mucosal Irritation

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