Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis.
Ontology highlight
ABSTRACT:
SUBMITTER: Facciorusso A
PROVIDER: S-EPMC7017079 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:OBJECTIVE:Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. We conducted network meta-regression within a Bayesian framework to compare and rank different treatment strategies for HCC through direct and indirect evidence from international studies. METHODS AND ANALYSES:We pooled the OR for 1-year, 3-year and 5-year overall survival, based on lesions of size ? 3?cm, 3-5?cm and ?5?cm, using five therapeutic options including resection (RES), radiofrequency ablation (RFA), microwave ablation (MWA), transcatheter arterial chemoembolisation (TACE) plus RFA (TR) and percutaneous ethanol injection (PEI). RESULTS:We identified 74 studies, including 26?944 patients. After adjustment for study design, and in the full sample of studies, the treatments were ranked in order of greatest to least benefit as follows for 5?year survival: (1) RES, (2) TR, (3) RFA, (4) MWA and (5) PEI. The ranks were similar for 1- and 3-year survival, with RES and TR being the highest ranking treatments. In both smaller (<3?cm) and larger tumours (3-5?cm), RES and TR were also the two highest ranking treatments. There was little evidence of inconsistency between direct and indirect evidence. CONCLUSION:The comparison of different treatment strategies for HCC indicated that RES is associated with longer survival. However, many of the between-treatment comparisons were not statistically significant and, for now, selection of strategies for treatment will depend on patient and disease characteristics. Additionally, much of the evidence was provided by non-randomised studies and knowledge gaps still exist. More head-to-head comparisons between both RES and TR, or other approaches, will be necessary to confirm these findings.
| S-EPMC6196801 | biostudies-other
Project description:Background and aimImmune checkpoint inhibitors (ICIs) have been widely used in hepatocellular carcinoma (HCC), while only a subset of patients experience clinical benefit. We aimed to investigate the effects of viral etiology on response to ICIs in HCC and depict the tumor immune microenvironment (TIME) of virally infected and uninfected HCC.MethodsA systematic search was conducted in PubMed, Web of Science, Embase, and the Cochrane central register of controlled trials up to August 2021. Clinical trials reporting the efficacy of ICIs in HCC were eligible. Baseline characteristics including first author, year of publication, National Clinical Trials (NCT) registry number, study region, sample sizes, interventions, line of treatment, and viral status were extracted. Meta-analysis was conducted to generate combined odds ratios (ORs) with 95% confidence intervals (CI) based on random or fixed effect model, depending on heterogeneity. Tumor immune microenvironment was depicted using ESTIMATE and CIBERSORT algorithm.ResultsEight studies involving 1,520 patients were included. Combined data suggested that there was no significant difference of objective response rate (ORR) between virally infected HCC and non-viral HCC patients [OR = 1.03 (95% CI, 0.77-1.37; I2 = 30.9%, pH = 0.152)]. Similarly, difference was not observed on ORR between HBV-HCC and HCV-HCC patients [OR = 0.74 (95% CI, 0.52-1.06; I2 = 7.4%, pH = 0.374)]. The infiltration of immune cells in the tumor microenvironment did not differ by etiology except for M0 macrophages, M2 macrophages, regulatory T cells, naive B cells, follicular helper T cells, activated dendritic cells, activated mast cells, and plasma cells. Despite differences in infiltration observed in specific cell types, the immune score and stromal score were generally comparable among etiology groups.ConclusionViral etiology may not be considered as the selection criteria for patients receiving ICIs in HCC, and viral status has little impact on TIME remodeling during HCC tumorigenesis.
| S-EPMC8511422 | biostudies-literature
Project description:BackgroundNo trials have compared cabozantinib and regorafenib for the second-line treatment of advanced hepatocellular carcinoma (HCC).ObjectivesConduct a matching-adjusted indirect comparison (MAIC) of the efficacy and safety of second-line cabozantinib and regorafenib in patients with advanced HCC and disease progression after prior sorafenib.MethodsThe CELESTIAL and RESORCE trials were used for indirect comparison of second-line cabozantinib and regorafenib in advanced HCC. Population-level data were available for RESORCE, individual patient data (IPD) for CELESTIAL. To align with RESORCE, the CELESTIAL population was limited to patients who received first-line sorafenib only. To minimize potential effect-modifying population differences, the CELESTIAL IPD were weighted to balance the distribution of clinically relevant baseline characteristics with those of RESORCE. Overall survival (OS) and progression-free survival (PFS) were evaluated for the matching-adjusted second-line CELESTIAL population and compared with those for RESORCE using weighted Kaplan-Meier curves and parametric modeling. Rates of grade 3/4 treatment-emergent adverse events (TEAEs) affecting > 5% of patients in any study arm were compared.ResultsIn the matching-adjusted second-line populations (CELESTIAL, effective sample size = 266; RESORCE, n = 573), median (95% confidence interval) OS was similar for cabozantinib and regorafenib (11.4 [8.9-17.0] versus 10.6 [9.1-12.1] months; p = 0.3474, log-rank test). Median PFS was longer for cabozantinib than regorafenib (5.6 [4.9-7.3] versus 3.1 [2.8-4.2] months; p = 0.0005, log-rank test). There was a trend for lower rates of some grade 3/4 TEAEs with regorafenib than with cabozantinib, which may reflect the exclusion of sorafenib-intolerant patients from RESORCE but not from CELESTIAL, a difference that the MAIC methods could not remove. Only diarrhea rates were statistically significantly lower for regorafenib (p ≤ 0.001).ConclusionsCabozantinib may achieve similar OS and prolonged PFS compared with regorafenib in patients with progressive advanced HCC after prior sorafenib.
| S-EPMC7467441 | biostudies-literature
Project description:Background and aimsHepatocellular carcinoma (HCC) surveillance is associated with early tumor detection and improved survival; however, it is often underused in clinical practice. We aimed to characterize surveillance use among patients with cirrhosis and the efficacy of interventions to increase surveillance.Approach and resultsWe performed a systematic literature review using the MEDLINE database from January 2010 through August 2018 to identify cohort studies evaluating HCC surveillance receipt or interventions to increase surveillance in patients with cirrhosis. A pooled estimate for surveillance receipt with 95% confidence intervals was calculated. Correlates of surveillance use were defined from each study and prespecified subgroup analyses. Twenty-nine studies, with a total of 118,799 patients, met inclusion criteria, with a pooled estimate for surveillance use of 24.0% (95% confidence interval, 18.4-30.1). In subgroup analyses, the highest surveillance receipt was reported in studies with patients enrolled from subspecialty gastroenterology/hepatology clinics and lowest in studies characterizing surveillance in population-based cohorts (73.7% versus 8.8%, P < 0.001). Commonly reported correlates of surveillance included higher receipt among patients followed by subspecialists and lower receipt among those with alcohol-associated or nonalcoholic steatohepatitis (NASH)-related cirrhosis. All eight studies (n = 5,229) evaluating interventions including patient/provider education, inreach (e.g., reminder and recall systems), and population health outreach strategies reported significant increases (range 9.4%-63.6%) in surveillance receipt.ConclusionsHCC surveillance remains underused in clinical practice, particularly among patients with alcohol-associated or NASH-related cirrhosis and those not followed in subspecialty gastroenterology clinics. Interventions such as provider education, inreach including reminder systems, and population health outreach efforts can significantly increase HCC surveillance.
| S-EPMC7648722 | biostudies-literature
Project description:BackgroundTumour growth patterns have important implications for surveillance intervals, prognostication and treatment decisions but have not been well described for hepatocellular carcinoma (HCC). The aim of our study was to characterise HCC doubling time and identify correlates for indolent and rapid growth patterns.MethodsWe performed a systematic literature review of Medline and EMBASE databases from inception to December 2019 and national meeting abstracts from 2010 to 2018. We identified studies reporting HCC tumour growth or tumour volume doubling time (TVDT), without intervening treatment, and abstracted data to calculate TVDT and correlates of growth patterns (rapid defined as TVDT <3 months and indolent as TVDT >9 months). Pooled TVDT was calculated using a random-effects model.ResultsWe identified 20 studies, including 1374 HCC lesions in 1334 patients. The pooled TVDT was 4.6 months (95% CI 3.9 to 5.3 months I2=94%), with 35% classified as rapid, 27.4% intermediate and 37.6% indolent growth. In subgroup analysis, studies from Asia reported shorter TVDT than studies elsewhere (4.1 vs 5.8 months). The most consistent correlates of rapid tumour growth included hepatitis B aetiology, smaller tumour size (continuous), alpha fetoprotein doubling time and poor tumour differentiation. Studies were limited by small sample sizes, measurement bias and selection bias.ConclusionTVDT of HCC is approximately 4-5 months; however, there is heterogeneity in tumour growth patterns, including more aggressive patterns in Asian hepatitis B-predominant populations. Identifying correlates of tumour growth patterns is important to better individualise HCC prognostication and treatment decisions.
| S-EPMC7657990 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is an intractable public health threat worldwide, representing the second leading cause of cancer-related mortality, with limited early detection and therapeutic options. Recent findings have revealed that the susceptibility of HCC is closely related to microRNA (miRNA). We performed this systematic review with a network meta-analysis to investigated four single nucleotide polymorphisms (SNPs) that most regularly reported in miRNAs, exploring their involvement in HCC susceptibility and interaction with hepatitis B virus (HBV).MethodsDatabases were reviewed for related studies published up to May 2019 to identify all studies that compared genotypes of miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 with no language and date restrictions. A pairwise meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals incorporating heterogeneity to assess the relationship between four miRNA polymorphisms and HCC. To further clarify the effect of polymorphisms on HCC, a Bayesian network meta-analysis was conducted to combine the effective sizes of direct and indirect comparisons. Calculations were performed by R version 3.6.1 and STATA 14.0. All steps were performed according to PRISMA guidelines.ResultsA total of 20 studies were enrolled in this network meta-analysis, providing 5,337 hepatocellular carcinoma cases and 6,585 controls. All included studies had an acceptable quality. Pairwise meta-analysis demonstrated that miR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, while the other three SNPs were not found to have a significant association. In the analysis of HCC patients under different HBV infection status, only miR-196a2 revealed correlation of threefold risk. The network results showed no significant difference in the distribution of genotype frequencies except for miR-196a2, which appeared to have the highest superiority index when comparing and ranking four SNPs.ConclusionMiR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, especially for HBV- related HCC, and that individuals with TC/CC were more susceptible. No significant association was found in the other three miRNA genes. MiR-196a2 could serve as the best predictor of susceptibility in HCC.
| S-EPMC7851082 | biostudies-literature
Project description:We aimed to systematically evaluate the incidence of inadequate US in hepatocellular carcinoma (HCC) surveillance and determine the risk factors. Original studies reporting the incidence or risk factors for inadequate US were identified in MEDLINE, EMBASE, and the Cochrane database. The pooled incidence of inadequate US was calculated using a random effects model, and subgroup analyses were performed. The pooled odds ratio (OR) was calculated for each risk factor for inadequate US. Six eligible articles were identified from 756 screened articles (4250 patients). The pooled incidence of inadequate US was 21.5%. Significantly higher rates of inadequate US were noted in studies including patients with and without hepatic observations compared with those evaluating only patients with hepatic observations (23.2% vs. 18.8%), studies using US alone compared with US plus alpha-fetoprotein (28.0% vs. 20.8%), and those using pathology and imaging as a reference standard compared with imaging only (23.2% vs. 17.9%). Nonalcoholic steatohepatitis (OR = 2.3 (1.07-4.84)), Child-Pugh B cirrhosis (OR = 2.2 (1.10-4.37)), and high body mass index (OR = 2.2 (1.12-4.24)) were significant risk factors for inadequate US (p ≤ 0.04). In patients at risk of HCC, 21.5% of US surveillance was inadequate. An alternative surveillance modality might be considered in patients with risk factors.
| S-EPMC8397222 | biostudies-literature
Project description:BackgroundThe present comparative meta-analysis was conducted to evaluate the cardiovascular events of regorafenib in patients with solid tumors.MethodsEligible studies from MEDLINE, Google Scholar, Cochrane Library, Clinical key, EBSCO publishing and Ovid, which had reported cardiovascular adverse events potentially caused by regorafenib were absorbed. Data of clinical characteristics and cardiovascular events including hypertension, hemorrhage, thrombosis, and heart failure were extracted from selected literatures for the final analysis. Pooled analysis of cardiovascular adverse events was developed by relative risks (RRs) and corresponding 95% confidence intervals (CIs) with software STATA 13.0 and RevMan 5.3.ResultsThirty studies including 3813 patients were fit into analysis. The incidences of cardiovascular events of all-grade were: hypertension, 36.8% (95% CI, 29.8%-43.8%), hemorrhage, 8.6% (95% CI, 3.2%-14%), thrombosis, 1.4% (95% CI, 0.1%-2.8%), and heart failure, 2.9% (95% CI, 0.3%-5.6%). The incidences of cardiovascular events of high-grade were: hypertension, 9.9% (95% CI, 7.4%-12.4%), hemorrhage, 1.2% (95% CI, 0.3%-2.2%), thrombosis, 1.6% (95% CI, 0.2%-3.4%), and heart failure, 2.9% (95% CI, 0.3%-5.6%). The RRs and their 95% CIs of all-grade cardiovascular events among patients treated with regorafenib were: hypertension, 4.10 (95% CI, 3.07-5.46; P?<?.00001), hemorrhage, 2.71 (95% CI, 1.45-5.08; P?=?.002), thrombosis, 1.27 (95% CI, 0.49-3.27; P?=?.62), and heart failure, 0.79 (95% CI, 0.16-3.94; P?=?.77). The RRs and their 95% CIs of high-grade cardiovascular events among patients treated with regorafenib were: hypertension, 5.82 (95% CI, 3.46-9.78; P?<?.00001), hemorrhage, 0.90 (95% CI, 0.50-1.61; P?=?.72), thrombosis, 1.28 (95% CI, 0.48-3.41; P?=?.62), and heart failure, 1.15 (95% CI, 0.23-5.69; P?=?.86), respectively.ConclusionThe present meta-analysis has demonstrated that regorafenib is associated with an increasing risk of hypertension at all-grade and high-grade, as well as hemorrhage at all-grade. Adequate awareness of cardiovascular adverse events of regorafenib should be established for clinicians.
| S-EPMC6203579 | biostudies-literature
Project description:Background:The evidence base for optimum third-line therapy for metastatic colorectal cancer (mCRC) is not conclusive. Recent studies have demonstrated the efficacy of regorafenib as third-line therapy in mCRC. This indirect meta-analysis compared the efficacy and safety of regorafenib with other available third-line therapies for mCRC. Methods:A literature search for randomized controlled trials (RCTs) was conducted in PubMed, Embase, and Cochrane Library for studies evaluating the efficacy and safety of fruquintinib, regorafenib, TAS-102, and nintedanib as third-line therapies in patients with mCRC. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes, while objective response rate (ORR) and safety were the secondary outcomes. Hazard ratio (HR) and relative risk (RR) with their respective 95% confidence interval (CI) were used for analysis of survival, clinical response, and safety data. An adjusted indirect meta-analysis with placebo as the common comparator was performed. Results:We identified eight RCTs comparing regorafenib (two studies), fruquintinib (two studies), TAS-102 (three studies), and nintedanib (one study) against placebo. The OS with regorafenib was significantly better when compared with nintedanib (HR?=?0.66; 95% CI: 0.45, 0.95, p?=?0.02) but was similar to that of fruquintinib (HR?=?1.01; 95% CI: 0.67, 1.52, p?=?0.94) and TAS-102 (HR?=?0.97; 95% CI: 0.68, 1.38, p?=?0.88). The PFS and ORR for regorafenib were slightly better than those of TAS-102 (PFS: HR?=?0.86, 95% CI: 0.54, 1.37, p?=?0.5; ORR: RR?=?1.13, 95% CI: 0.11, 11.05, p?=?0.92) and nintedanib (PFS: HR?=?0.68, 95% CI: 0.42, 1.10, p?=?0.12; ORR: not reported) but were lower than those for fruquintinib (PFS: HR?=?1.53, 95% CI: 0.93, 2.52, p?=?0.08; ORR: RR?=?0.68269, 95% CI: 0.045, 10.32, p?=?0.79). Safety analysis showed that the RR of adverse events (AEs) was lesser in patients treated with regorafenib in comparison with that in patients treated with fruquintinib, but was similar to that in patients treated with nintedanib and TAS-102. Conclusion:Regorafenib has efficacy similar to that of TAS-102 and better safety when compared with fruquintinib. Considering the mechanism of action of regorafenib, which targets multiple factors in the angiogenic pathway, it could be an ideal option for treatment in the beyond second-line setting.
| S-EPMC7364795 | biostudies-literature
Project description:BackgroundThe present network meta-analysis was conducted to perform an indirect comparison among ramucirumab, regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma (HCC) progressed on sorafenib treatment.MethodsA systematic review through Medline, Embase, and Cochrane library was developed, with eligible randomized clinical trials been included. Hazard ratios (HRs) including progression-free survival (PFS), overall survival (OS), odds ratios of disease control rate (DCR), objective response rate (ORR), and adverse events were compared indirectly with network meta-analysis using random model in software STATA version 13.0.ResultsA total of 4 randomized clinical trials including 2137 patients met the eligibility criteria and enrolled. Indirect comparisons showed that there was no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among agents of regorafenib, cabozantinib, and ramucirumab in advanced HCC patients with elevated α-fetoprotein (AFP) (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib was the only agent associated with significant superiority in OS, compared with placebo (hazard ratio 0.67, 95% CI, 0.50-0.90).ConclusionsThe present network meta-analysis revealed that there might be no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among regorafenib, cabozantinib, or ramucirumab in advanced HCC patients with elevated AFP (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib might be associated with significant superiority in OS, compared to placebo, which need further investigation in clinical practice.
| S-EPMC8462645 | biostudies-literature