Dataset Information

Efficacy and Safety Associated With Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma: A Meta-analysis.

ABSTRACT:

Importance

Immune checkpoint inhibitors (ICIs) have yielded conflicting results in hepatocellular carcinoma (HCC). The overall effect of ICIs compared with standard therapies in unresectable HCC requires more research.

Objective

To estimate the efficacy and safety associated with ICIs compared with standard therapies in patients with unresectable HCC.

Data sources

PubMed, Cochrane Library, Web of Science, Latin American and Caribbean Health Sciences Literature, and American Society of Clinical Oncology and European Society of Medical Oncology meeting proceedings were systematically searched. Reference lists from studies selected by electronic searching were manually searched to identify additional relevant studies. The search included literature published or presented from February 2010 to February 2020.

Study selection

From December 2019 to February 2020, independent reviewers evaluated each database, scanning the title, abstract, and keywords of every record retrieved. Full articles were further assessed if the information given suggested that the study was a randomized clinical trial (RCT) comparing ICIs vs standard therapies in the treatment of unresectable HCC.

Data extraction and synthesis

The full text of the resulting studies and extracted data were reviewed independently according to PRISMA guidelines. Summary hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were calculated by a random-effects model. The likelihood of ICIs being associated with overall response rate (ORR) and treatment-related adverse events (TRAEs) was expressed by odds ratios (ORs) using a random-effects model.

Main outcomes and measures

The main outcomes were OS, PFS, ORR, and TRAEs.

Results

Of 1836 studies yielded by the search, 3 were retained, totaling 1657 patients (985 treated with ICIs vs 672 receiving standard treatment). Two studies evaluated ICIs as monotherapy, and 1 study investigated the combination of ICIs with bevacizumab. Compared with standard therapies (sorafenib in first-line therapy or placebo in second-line therapy), ICIs were associated with significantly improved OS (HR, 0.75; 95% CI, 0.62-0.92; P = .006), PFS (HR, 0.74; 95% CI, 0.56-0.97; P = .03), and ORR (OR, 2.82; 95% CI 2.02-3.93; P < .001). The probability of grade 3 or 4 TRAEs was lower with ICIs than with sorafenib (OR, 0.44; 95% CI, 0.20-0.96; P = .04).

Conclusions and relevance

This meta-analysis found superior efficacy and safety associated with ICIs compared with standard therapies and highlights the survival benefit associated with the combination of antiangiogenic therapy with ICIs in first-line systemic therapy of unresectable HCC.

SUBMITTER: Jacome AA

PROVIDER: S-EPMC8649834 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundHepatocellular carcinoma (HCC) is one of the cancers with the highest morbidity and mortality. Sorafenib used to be the main treatment for unresectable HCC patients. However, regimens based on immune checkpoint inhibitors (ICIs) have attracted attention in recent years because of their reported benefits. This study aimed to evaluate the efficacy and safety of monotherapy and combination therapy of ICIs as first-line treatment for unresectable HCC patients by conducting a systematic review, meta-analysis, and network meta-analysis.MethodsStudies published up to 11st August 2022 were searched from 4 commonly used databases, including PubMed, Web of Science, Embase, and Clinical trials.gov. All eligible clinical trials were included. Data about reported objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were extracted.ResultsOf the 8579 studies retrieved, 24 met the inclusion criteria. In patients with unresectable HCC taking ICIs-based therapy as first-line treatment, the pooled result of median PFS and median OS was 5.76 months (95% CI 4.82-6.69) and 16.35 months (95% CI 15.19-17.51) The ORR and DCR were 25.1% (95% CI 20.8-29.5%) and 75.2% (95% CI 70.3-80.2%) measured by RECIST v1.1 or 40.2% (95% CI 31.7-48.6%) with 75.2% (95% CI 68.3-82.1%) measured by mRECIST v1.1. Compared to sorafenib, ICIs-based therapy significantly prolonged OS. The combination treatment of sintilimab plus IBI305 had the highest ORR, while atezolizumab plus bevacizumab had the highest DCR. The pooled incidence of any grade TRAEs was 82.3% (95% CI 73.9-90.7%), with highest incidence appeared in dysphonia.ConclusionsThis study demonstrated that first-line ICIs-based therapies could provide survival benefits for patients with unresectable HCC, with manageable TRAEs. The potential of combination treatment to become the new treatment trend in clinical practice is promising.

Project description:BackgroundThe combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic agents has shown promising efficacy in unresectable hepatocellular carcinoma (HCC), but until now no clinical prognostic models or predictive biomarkers have been established.MethodsFrom 2016 to 2021, a total of 258 HCCs treated with ICIs and tyrosine kinase inhibitors (TKIs) were retrospectively enrolled, as the study cohort. Patients' baseline data was extracted by least absolute and shrinkage selection operator (LASSO) and Cox regression. Finally, a prognostic model in the form of nomogram was developed. Model performance was assessed in terms of discrimination, calibration, and clinical utility. A 5-fold cross-validation was used to evaluate the internal repeatability of the model. In addition, the patient cohort was divided into three subgroups according to nomogram scores. Their survivals were estimated by Kaplan-Meier methods and the differences were analyzed using log-rank tests.ResultsSeven clinical parameters were selected: Eastern Cooperative Oncology Group performance status (ECOG PS), combination of transarterial chemoembolization (TACE), extrahepatic metastasis (EHM), platelet to lymphocyte ratio (PLR), alanine aminotransferase (ALT), alpha-fetoprotein (AFP), and Child-Pugh score. The model had an area under the curve (AUC) of 0.777 at 1 year and 0.772 at 2 years. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) showed that the discrimination, consistency and applicability of the model were good. In addition, cross-validation validated the discrimination of the model, and the C index value of the model is 0.7405. The median overall survival (OS) of the high-, medium- and low-risk subgroups was 7.58, 17.50 and 53.17 months, respectively, with a significant difference between the groups (P < 0.0001).ConclusionWe developed a comprehensive and simple prognostic model for the combination of ICIs plus TKIs. And it may predict the efficacy of the combination regimen for unresectable HCC.

Project description:PurposeThis study aimed to assess the efficacy and safety of a triple therapy that comprises transarterial chemoembolization (TACE), antiangiogenic-targeted therapy, and programmed death-1 (PD-1) inhibitors in a real-world cohort of patients with unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).MethodsConsecutive patients treated with TACE combined with antiangiogenic therapy and PD-1 inhibitors at the Eastern Hepatobiliary Surgery Hospital between June 2019 and May 2021 were enrolled. The baseline characteristics and treatment course of the patients were recorded. The tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and HCC-specific modified RECIST (mRECIST). The overall survival (OS) and progression-free survival (PFS) of the patients were analyzed using the Kaplan-Meier method. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.ResultsAs of the data cutoff on 30 August 2021, the median follow-up time was 10.0 (3.9-28.4) months. A total of 39 eligible patients were included. The objective response rate (ORR) and the disease control rate (DCR) were 35.9% and 74.4% according to the RECIST 1.1, and 48.7% and 84.6% according to mRECIST criteria, respectively. The median OS and PFS were 14.0 and 9.2 months, respectively. Moreover, 34 (87.2%) patients experienced at least one treatment-related AE and 8 (20.5%) patients experienced grade 3/4 treatment-related AEs. The most common treatment- and laboratory-related AEs were hypertension (46.2%) and decreased albumin (53.8%), respectively. No treatment-related mortality occurred during the study period.ConclusionsTACE combined with antiangiogenic-targeted therapy and immune checkpoint inhibitors may have promising anticancer activity in unresectable HCC patients with PVTT. AEs were manageable, with no unexpected overlapping toxicities.

Project description:Background & aimsWe investigated the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with hepatocellular carcinoma (HCC) who received ICI-based therapies in a previous systemic line.MethodsIn this international, retrospective multicenter study, patients with HCC who received at least two lines of ICI-based therapies (ICI-1, ICI-2) at 14 institutions were eligible. The main outcomes included best overall response and treatment-related adverse events.ResultsOf 994 ICI-treated patients screened, a total of 58 patients (male, n = 41; 71%) with a mean age of 65.0±9.0 years were included. Median systemic treatment lines of ICI-1 and ICI-2 were 1 (range, 1-4) and 3 (range, 2-9), respectively. ICI-based therapies used at ICI-1 and ICI-2 included ICI alone (ICI-1, n = 26, 45%; ICI-2, n = 4, 7%), dual ICI regimens (n = 1, 2%; n = 12, 21%), or ICI combined with targeted therapies/anti-VEGF (n = 31, 53%; n = 42, 72%). Most patients discontinued ICI-1 due to progression (n = 52, 90%). Objective response rate was 22% at ICI-1 and 26% at ICI-2. Responses at ICI-2 were also seen in patients who had progressive disease as best overall response at ICI-1 (n = 11/21; 52%). Median time-to-progression at ICI-1 and ICI-2 was 5.4 (95% CI 3.0-7.7) months and 5.2 (95% CI 3.3-7.0) months, respectively. Treatment-related adverse events of grade 3-4 at ICI-1 and ICI-2 were observed in 9 (16%) and 10 (17%) patients, respectively.ConclusionsICI rechallenge was safe and resulted in a treatment benefit in a meaningful proportion of patients with HCC. These data provide a rationale for investigating ICI-based regimens in patients who progressed on first-line immunotherapy in prospective trials.Impact and implicationsTherapeutic sequencing after first-line immune checkpoint inhibitor (ICI)-based therapy for advanced hepatocellular carcinoma (HCC) remains a challenge as no available second-line treatment options have been studied in immunotherapy-pretreated patients. Particularly, the role of ICI rechallenge in patients with HCC is unclear, as data from prospective trials are lacking. We investigated the efficacy and safety of ICI-based regimens in patients with HCC pretreated with immunotherapy in a retrospective, international, multicenter study. Our data provide the rationale for prospective trials investigating the role of ICI-based regimens in patients who have progressed on first-line immunotherapy.