Real-world efficiency of lenvatinib plus PD-1 blockades in advanced hepatocellular carcinoma: an exploration for expanded indications

Sun, Xuqi; Zhang, Qi; Mei, Jie; Yang, Ziliang; Chen, Minshan; Liang, Tingbo

doi:10.1186/s12885-022-09405-7

Cited by 27 publications

(21 citation statements)

References 29 publications

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“…For the tumor response, the RESCUE trial ( 6 ) disclosed an ORR of 34.3% and a DCR of 77.1% following combined apatinib and camrelizumab therapy. The TACE + AC group had a greater ORR compared to those reported by the IMbrave150 trial ( 7 ) (atezolizumab plus bevacizumab: ORR = 33.2%), the phase 1b KEYNOTE-524 trial ( 22 ) (lenvatinib plus pembrolizumab: ORR = 46.0%), and the ORIENT-32 trial (sintilimab plus bevacizumab: ORR = 24%); this was likely because the addition of TACE is thought to be related to immune activation and can induce low expression of Tregs via modulating pro-inflammatory pathways. In our study, the CR, ORR, and DCR rates of the TACE + AC group were numerically greater than those of the TACE + A group (11.8% vs. 5.9%, 55.9% vs. 51.5%, and 79.4% vs. 72.1%, respectively), although the difference did not reach statistical significance.…”

Section: Discussionmentioning

confidence: 79%

Transarterial chemoembolization plus apatinib with or without camrelizumab for unresected hepatocellular carcinoma: A two-center propensity score matching study

Zhu

Ma²,

Yang³

et al. 2022

Front. Oncol.

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PurposeTo compare the effectiveness and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab with those of TACE as well as apatinib among patients with unresectable hepatocellular carcinoma (HCC).Materials and methodsThe data of patients with unresectable HCC (uHCC) who received TACE-apatinib-camrelizumab combination (TACE + AC group) and TACE-apatinib combination (TACE + A group) were collected from two centers between January 2018 and January 2022. Propensity score matching (PSM) was conducted to diminish the bias between the two groups. The primary outcome measures of the study were overall survival (OS) and progression-free survival (PFS), and the secondary outcome measures were response rate (ORR), disease control rate (DCR), and adverse events (AEs).ResultsA total of 102 patients were enrolled in this study after PSM, with 34 patients in the TACE + AC group and 68 patients in the TACE + A group. Compared to the TACE + A group, TACE + AC had a significantly longer median OS (25.5 months, interquartile range [IQR], 23.5–33.0) than 18.5 months (IQR, 13.0–25.0; P = 0.001). Similarly, the PFS of the TACE + AC group was significantly improved (14.0 months, IQR, 9.0–NA) compared to that of the TACE + A group (5.0 months, IQR, 2.5–9.0; P = 0.001). The ORR rates (55.9% vs. 51.5%), and DCR rates (79.4% vs. 72.1%) were comparable between groups (P > 0.05). All treatment-related adverse events were tolerable and manageable, and no serious adverse events were observed.ConclusionTACE combined with apatinib plus camrelizumab demonstrated superior efficacy to TACE plus apatinib for patients with unresectable HCC. The two combination therapies showed similar safety profiles.

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Section: Discussionmentioning

confidence: 79%

Transarterial chemoembolization plus apatinib with or without camrelizumab for unresected hepatocellular carcinoma: A two-center propensity score matching study

Zhu

Ma²,

Yang³

et al. 2022

Front. Oncol.

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“…Study characteristics are shown in eTable 1 in Supplement 1. In summary, 19 of the 22 studies were retrospective, 3 were prospective, 6 evaluated nivolumab, 4 evaluated nivolumab and pembrolizumab, 1 evaluated camrelizumab, 1 evaluated pembrolizumab, 5 evaluated atezolizumab, and the remaining 5 did not describe detailed agents . The median patient age ranged from 53 to 73 years among included studies.…”

Section: Resultsmentioning

confidence: 99%

Immune Checkpoint Inhibitors for Child-Pugh Class B Advanced Hepatocellular Carcinoma

Xie,

Yeo,

Scheiner

et al. 2023

JAMA Oncol

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ImportanceImmune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced hepatocellular carcinoma (HCC). However, data on ICI therapy in patients with advanced HCC and impaired liver function are scarce.ObjectiveTo conduct a systematic review and meta-analysis to determine the efficacy and safety of ICI treatment for advanced HCC with Child-Pugh B liver function.Data SourcesPubMed, Embase, Web of Science, and Cochrane Library were searched for relevant studies from inception through June 15, 2022.Study SelectionRandomized clinical trials, cohort studies, or single-group studies that investigated the efficacy or safety of ICI therapy for Child-Pugh B advanced HCC were included.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline was followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 &gt; 50%); otherwise, a fixed-effect model was used.Main Outcomes and MeasuresThe objective response rate (ORR) and overall survival (OS) were considered to be the primary efficacy outcomes of ICI treatment for Child-Pugh B advanced HCC, and the incidence of treatment-related adverse events (trAEs) was set as the primary measure for the safety outcome.ResultsA total of 22 studies including 699 patients with Child-Pugh B and 2114 with Child-Pugh A advanced HCC comprised the analytic sample (median age range, 53-73 years). Upon pooled analysis, patients treated with ICIs in the Child-Pugh B group had an ORR of 14% (95% CI, 11%-17%) and disease control rate (DCR) of 46% (95% CI, 36%-56%), with a median OS of 5.49 (95% CI, 3.57-7.42) months and median progression-free survival of 2.68 (95% CI, 1.85-3.52) months. The rate of any grade trAEs in the Child-Pugh B group was 40% (95% CI, 34%-47%) and of grade 3 or higher trAEs was 12% (95% CI, 6%-23%). Compared with the Child-Pugh A group, the ORR (odds ratio, 0.59; 95% CI, 0.43-0.81; P &lt; .001) and DCR (odds ratio, 0.64; 95% CI, 0.50-0.81; P &lt; .001) were lower in the Child-Pugh B group. Child-Pugh B was independently associated with worse OS in patients with advanced HCC treated with ICIs (hazard ratio, 2.72 [95% CI, 2.34-3.16]; adjusted hazard ratio, 2.33 [95% CI, 1.81-2.99]). However, ICIs were not associated with increased trAEs in the Child-Pugh B group.Conclusions and RelevanceThe findings of this systematic review and meta-analysis suggest that although the safety of ICI treatment was comparable between patients with HCC with vs without advanced liver disease and the treatment resulted in a significant number of radiologic responses, survival outcomes are still inferior in patients with worse liver function. More study is needed to determine the effectiveness of ICI treatment in this population.

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“… 25 Interestingly, we noticed that a recently reported retrospective study initiated by Sun et al explored the real-world effectiveness of lenvatinib plus PD-1 inhibitors in advanced HCC. 26 A total of 84 patients with HCC receiving lenvatinib plus PD-1 blockades were recruited for retrospective analysis, including 31 patients with tumor occupation ≥50% and 30 patients with Vp4 invasion, which resulted in an ORR of 20.2%, a DCR of 40.5%, a median PFS of 6.6 months and a median OS of 11.4 months. Obviously, the clinical outcomes in this study seemed to be worse compared with those in our study.…”

Section: Discussionmentioning

confidence: 99%

“… 34 Therefore, patients enrolled in this study were representative of the patients with HCC in China and the finding that patients with HBV infection might benefit from lenvatinib plus PD-1 blockades were in concert with the study reported previously. 26 Collectively, clinical outcomes of lenvatinib plus PD-1 blockades among patients with unresectable advanced HCC should be elucidated in prospective clinical trials in the future.…”

Section: Discussionmentioning

confidence: 99%

Feasibility and Tolerability of Lenvatinib, Plus PD-1 Blockades for Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Exploratory Study

Meng¹,

Jia²,

Xu³

et al. 2022

CMAR

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Objective Lenvatinib was the standard first-line therapy for patients with unresectable HCC. PD-1 blockades demonstrated promising efficacy for patients with previously-treated HCC. Therefore, this study was to investigate the feasibility and tolerability of lenvatinib plus PD-1 blockades for patients with unresectable HCC retrospectively. Methods A total of 37 patients with unresectable HCC who received lenvatinib plus PD-1 blockades in first-line setting were included in this study retrospectively. Efficacy of the patients was evaluated with the change of target lesion using mRECIST criteria per investigator and all the subjects were followed up regularly. Adverse reactions were collected and documented. Exploratory analysis between prognosis and baseline characteristics was performed using log rank test and multivariate analysis were performed using Cox regression analysis. Results The best overall response of the 37 patients suggested that complete response was observed in one patient, partial response was noted in 11 patients, stable disease was noted in 16 patients and 9 patients had progressive disease, which yielded an objective response rate (ORR) of 32.4% (95%CI: 18.0–49.8) and a disease control rate (DCR) of 75.7% (95%CI: 58.8–88.2). Furthermore, the median progression-free survival (PFS) of the 37 patients with advanced HCC was 8.3 months (95%CI: 3.34–13.26). And the median overall survival (OS) was 17.8 months (95%CI: 7.19–28.41). In addition, the median duration of response (DoR) in 12 patients with response was 9.6 months (95%CI: 3.03–16.17). Furthermore, adverse reactions that were attributed to the combination administration were detected in 36 patients (97.3%), among whom a total of 22 patients (59.5%) were observed of the grade ≥3 adverse reactions. And the most common adverse reactions were hypertension, fatigue, nausea and vomiting, and hepatotoxicity. Conclusion Lenvatinib plus PD-1 blockades demonstrated promising anticancer activity and acceptable toxicity for patients with unresectable HCC. And the conclusion should be validated in prospective clinical trials subsequently.

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Real-world efficiency of lenvatinib plus PD-1 blockades in advanced hepatocellular carcinoma: an exploration for expanded indications

Cited by 27 publications

References 29 publications

Transarterial chemoembolization plus apatinib with or without camrelizumab for unresected hepatocellular carcinoma: A two-center propensity score matching study

Transarterial chemoembolization plus apatinib with or without camrelizumab for unresected hepatocellular carcinoma: A two-center propensity score matching study

Immune Checkpoint Inhibitors for Child-Pugh Class B Advanced Hepatocellular Carcinoma

Feasibility and Tolerability of Lenvatinib, Plus PD-1 Blockades for Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Exploratory Study

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