Dataset Information

Lenvatinib in combination with transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma (uHCC): a retrospective controlled study.

ABSTRACT:

Purpose

To compare the efficacy and safety of combined treatment with lenvatinib and transarterial chemoembolization (TACE) versus TACE only in patients with unresectable hepatocellular carcinoma (uHCC).

Methods

Of the 120 patients enrolled in this study, 60 patients received treatment with TACE only, and 60 patients received TACE plus lenvatinib. We retrospectively compared the clinical outcomes including overall survival (OS), progression-free survival (PFS), and tumor response between the two groups. Both PFS and tumor response were based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Adverse events were analyzed to assess the safety profiles.

Results

The 1-year and 2-year OS rates were significantly higher in the TACE + lenvatinib group (88.4% and 79.8%) than that in the TACE group (79.2% and 49.2%, p = 0.047). A similar PFS benefit was observed in the TACE + lenvatinib group (1-y PFS rate: 78.4% vs. 64.7%, 2-y PFS rate: 45.5% vs. 38.0%, p < 0.001). The best overall objective response rate (ORR) was also better with TACE + lenvatinib treatment (ORR: 68.3% vs. 31.7%, p < 0.001) and disease control rate (DCR) numerically increased in the TACE + lenvatinib treatment (93.3% vs. 86.7%, p = 0.224). Patients' liver function remained comparable to baseline in the TACE + lenvatinib group. The most common adverse events were decreased albumin (55.0%), hypertension (48.3%) and decreased platelet count (46.7%) in the TACE + lenvatinib group.

Conclusions

Combination treatment with TACE and lenvatinib may significantly improve clinical outcomes over TACE monotherapy with a manageable safety profile for unresectable HCC. The efficacy of the combination treatment should be validated in prospective studies with a large sample size.

SUBMITTER: Fu Z

PROVIDER: S-EPMC8286947 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe combination of tyrosine kinase inhibitors (TKIs) and transarterial chemoembolization (TACE) fulfills an important role in the treatment of unresectable hepatocellular carcinoma (uHCC). Among the combination therapies, both lenvatinib and sorafenib combined with TACE are recommended as first-¬line treatments for uHCC. However, at present, limited data are available concerning the efficacy and safety of these two combination therapies in uHCC.MethodsA detailed systematic search for studies on lenvatinib plus TACE (LEN+TACE) and sorafenib plus TACE (SOR+TACE) was conducted in the online databases PubMed, Embase and The Cochrane Library. The outcome data including overall survival (OS), progression free survival (PFS), time to progression (TTP), tumor response and adverse events (AEs), were independently extracted by two authors in a standardized way.ResultsOne randomized controlled trial and five cohort studies with 598 patients (LEN+TACE: 261, SOR+TACE: 337) were included in the meta-analysis. A higher rate of odds ratio (OR) for the objective response rate (ORR) [OR: 3.63; 95% confidence intervals (95% CI): 1.89-6.95; I squared statistic (I2) = 57%, P < 0.001] and disease control rate (DCR) (OR: 3.78; 95% CI: 2.00-7.16; I2 = 52%, P = 0.0001) were observed in the LEN+SOR group compared with the SOR+TACE group. The LEN+TACE group also had significant longer OS [hazard ratio (HR): 0.67; 95% CI: 0.52-0.85; I2 = 1%, P = 0.001], PFS (HR: 0.49; 95% CI: 0.38-0.62; I2 = 0%, P? 0.001) and TTP (HR: 0.62; 95% CI: 0.45-0.84; I2 = 0%, P = 0.002) compared with the SOR+TACE group. The incidence of hypertension (OR: 3.05; 95% CI: 1.45-6.39; P = 0.003) and proteinuria (OR: 5.25; 95% CI: 1.73-15.89; P = 0.003) were significantly higher in the LEN+TACE group than SOR+TACE group, while LEN+TACE group exhibited a lower rate of hand-foot-skin reaction (HFSR) (OR: 0.51; 95% CI: 0.27-0.95; P = 0.03) compared with the SOR+TACE group.ConclusionThe combination therapy of LEN+TACE showed significant superiority compared with SOR+TACE in terms of its efficacy for patients with uHCC. SOR+TACE should be recommended as a replacement therapy when serious AEs occur during the administration of LEN+TACE as the combination therapy.

Project description:BackgroundLenvatinib and transarterial chemoembolization (TACE) are first-line treatments for unresectable hepatocellular carcinoma (HCC), but the objective response rate (ORR) is not satisfactory. We aimed to predict the response to lenvatinib combined with TACE before treatment for unresectable HCC using machine learning (ML) algorithms based on clinical data.MethodsPatients with unresectable HCC receiving the combination therapy of lenvatinib combined with TACE from two medical centers were retrospectively collected from January 2020 to December 2021. The response to the combination therapy was evaluated over the following 4-12 weeks. Five types of ML algorithms were applied to develop the predictive models, including classification and regression tree (CART), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost), random forest (RF), and support vector machine (SVM). The performance of the models was assessed by the receiver operating characteristic (ROC) curve and area under the receiver operating characteristic curve (AUC). The Shapley Additive exPlanation (SHAP) method was applied to explain the model.ResultsA total of 125 unresectable HCC patients were included in the analysis after the inclusion and exclusion criteria, among which 42 (33.6%) patients showed progression disease (PD), 49 (39.2%) showed stable disease (SD), and 34 (27.2%) achieved partial response (PR). The nonresponse group (PD + SD) included 91 patients, while the response group (PR) included 34 patients. The top 40 most important features from all 64 clinical features were selected using the recursive feature elimination (RFE) algorithm to develop the predictive models. The predictive power was satisfactory, with AUCs of 0.74 to 0.91. The SVM model and RF model showed the highest accuracy (86.5%), and the RF model showed the largest AUC (0.91, 95% confidence interval (CI): 0.61-0.95). The SHAP summary plot and decision plot illustrated the impact of the top 40 features on the efficacy of the combination therapy, and the SHAP force plot successfully predicted the efficacy at the individualized level.ConclusionsA new predictive model based on clinical data was developed using ML algorithms, which showed favorable performance in predicting the response to lenvatinib combined with TACE for unresectable HCC. Combining ML with SHAP could provide an explicit explanation of the efficacy prediction.