Efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma

Marta, Guilherme Nader; Fonseca, Leonardo Gomes da; Braghiroli, Maria Ignez; Moura, Fernando; Hoff, Paulo M.; Sabbaga, Jorge

doi:10.6061/clinics/2021/e2498

Cited by 5 publications

(7 citation statements)

References 32 publications

(41 reference statements)

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“…This could be attributed to patients with advanced age being vulnerable to the toxicity of anti-cancer agents 35 . Although some previous reports revealed that MTA-monotherapy could be used safely in elderly patients with advanced HCC 36 – 38 , there are few reportson whether the impact of advanced age is how to influence in sequential systemic therapy. In this study, we found that the incidence of fatigue, appetite loss were significantly higher in the ≥ 75 years group compared to in the < 75 years group ( p = < 0.001) in the first-line, and second line therapy, respectively (Supplementary Tables 1 and 2 ).…”

Section: Discussionmentioning

confidence: 99%

Deterioration of liver function and aging disturb sequential systemic therapy for unresectable hepatocellular carcinoma

Shimose

Hiraoka

Tanaka³

et al. 2022

Sci Rep

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This study aimed to investigate the clinical characteristics of patients with unresectable hepatocellular carcinoma (HCC), who were eligible for sequential systemic therapy. We evaluated 365 patients with HCC who underwent systemic therapy after 2017. The overall survival (OS) was 13.7 months, 19.2 months, and 35.6 months in the first-line, second-line, and third-line or later therapy groups, respectively. Multivariate analysis revealed that the modified-albumin-bilirubin (m-ALBI) grade, macrovascular invasion, extrahepatic spread, discontinuation due to adverse events (AEs), and sequential therapy were independent factors for OS. At the end of each therapy, the ALBI score was significantly worse among patients with discontinuation due to AEs than among those without. The conversion rate to second-line and third-line therapy among patients with discontinuation due to AEs was significantly lower than that among patients without (30.4% vs. 69.2%, p < 0.001; 6.7% vs. 58.3%; p < 0.001, respectively). In the decision tree analysis, m-ALBI grade 1 or 2a and non-advanced age were selected splitting variables, respectively, for sequential systemic therapy. In conclusion, sequential therapy prolonged the OS of unresectable HCC. Additionally, good hepatic function and non-advanced age were clinically eligible characteristics for sequential systemic therapy.

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Section: Discussionmentioning

confidence: 99%

Deterioration of liver function and aging disturb sequential systemic therapy for unresectable hepatocellular carcinoma

Shimose

Hiraoka

Tanaka³

et al. 2022

Sci Rep

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“…5 To date, the application of first-line TKIs plus PD-1 inhibitors in uHCC patients has received the consensus of the Chinese hepatobiliary clinical experts [6][7][8] and is widely used in clinical practice. Although previous studies have clarified the efficacy and safety of sorafenib or lenvatinib monotherapy and A+T in aging patients with uHCC, [25][26][27][28] and the efficacy and potential downstaging and conversion ability of TKIs plus PD-1 inhibitors have been explored in previous studies, [9][10][11][12][13][14][15][16][17] whether aging patients would benefit from TKIs plus PD-1 inhibitors, especially for PD-1 inhibitors used in patients aged ≥75 years old, remains unclear before our study. In our study, we found median OS to Notes: *Including reactive cutaneous capillary endothelial proliferation (RCCEP) and immune-mediated rash.…”

Section: Discussionmentioning

confidence: 94%

“…Therefore, participants from clinical trials might not accurately represent realworld situation of elderly patients, especially for whose age is ≥75 years. [22][23][24] Although previous studies have already investigated the application of sorafenib, lenvatinib monotherapy, or A+T in elderly patients with uHCC, [25][26][27][28] whether this group of patients would benefit from sorafenib or lenvatinib plus PD-1 inhibitors, needs to be clarified. In order to explore the efficacy and safety of sorafenib-or lenvatinib-based combination therapy with PD-1 inhibitors in elderly patients with uHCC, we conducted this study.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of TKI Plus PD-1 Inhibitors in Elderly uHCC Patients: A Retrospective Study

Chen¹,

Jin²,

Zhao³

et al. 2022

JHC

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To explore the efficacy and safety of sorafenib-or lenvatinib-based combination therapy with PD-1 inhibitors in elderly patients aged ≥75 years with unresectable hepatocellular carcinoma (uHCC). Patients and Methods: Systemic therapy-naïve uHCC patients who received first-line sorafenib-or lenvatinib-based combination therapy with PD-1 inhibitors were continually reviewed. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) in accordance with the Response Evaluation Criteria in Solid Tumors version 1.1. Adverse events (AEs) and immune-related AEs (irAEs) were also evaluated. Groups and subgroups were separated at the ages of 65 and 75 years and compared with 1:1 matching. Results: Total 169 eligible patients were enrolled, including 24 aged ≥75 years. Median progression-free survival (PFS) and overall survival (OS) in these 24 elderly patients were 4.6 (95% CI: 2.6-6.6) months, and 17.0 (95% CI: 11.2-22.8) months, with 3-, 6-, 12month OS rate at 82.90%, 73.70%, and 57.50%. Age ≥75 years was confirmed to be a risk factor influencing PFS among patients aged ≥65 years. Adverse events (AEs) were recorded in all these 24 elderly patients, with seven patients experiencing immune-mediated AEs (irAEs). Nearly 30% of elderly patients stopped treatment due to AEs (16% of these due to irAEs). No statistical differences were found in all efficacy endpoints at the cutoff age of 65 years. Conclusion: For patients aged ≥75 years, application of PD-1 inhibitors in combination with sorafenib or lenvatinib is promising, but this has to be done with caution and needs to be confirmed by future prospective studies.

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“…The shorter survival in this international study could be due to the inclusion of an unspecified proportion of BCLC-D patients, who in our area were not administered sorafenib. In the observational studies published so far ( 6 , 7 , 12 , 13 , 15 , 20 – 24 ) median OS differs significantly across the treatment centres in different countries, ranging from a low of 5.8 months (95% CI: 4.4-7.2) in South Korea to a high of 14.3 months in Japan (95% CI: 9.2-19.4). None of these studies found differences in OS in the elderly in comparison with the youngest, even if a higher threshold of age (80 and 85 years old) was considered ( 6 , 7 , 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…One limitation of our study is not having included patients between the ages of 70-74. Several retrospective studies (albeit with small samples) have previously ruled out differences in tolerability between groups with HCC of different ages ( 6 , 7 , 12 , 13 , 19 , 20 ). Only one small retrospective study reported more AE (bleeding) in patients over 75 years old due to a greater exposure to antithrombotic drugs, and also a higher rate of treatment interruption in this subgroup due to AE ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

Survival and adverse events of elderly patients treated with sorafenib for hepatocellular carcinoma

Soria

Calvo²,

Casas³

et al. 2022

Front. Oncol.

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IntroductionThe first-line treatment for advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab, but its availability is not universal and elderly patients are underrepresented in clinical trials. There is little evidence of efficacy and tolerability in elderly patients under systemic treatment. The aims of this study were to characterize the profile of elderly patients treated with sorafenib, assess their survival and safety profile in order to extrapolate their eligibility for systemic treatment.MethodsRetrospective multicentre study of HCC patients aged ≥75 years old treated with sorafenib from January 2008 to December 2019. Demographic data, baseline characteristics, and variables related to HCC and sorafenib were recorded. Overall survival (OS) and safety were analyzed.ResultsThe study included 206 patients from 11 hospitals, median age 77.9 years; 71.4% men and 62.6% stage Barcelona Clinic Liver Cancer- C (BCLC-C). The main causes of cirrhosis were hepatitis C (60.7%) and alcohol (14.7%). Most patients (84.5%) started with sorafenib 800mg and 15.5% at lower dosage. Arterial hypertension (AHT) (74.2 vs 62.2%; standardized mean differences (STD): 26) and baseline ECOG-PS>0 (45.3 vs 34.7%; STD: 38.2) differed significantly between patients receiving low and full doses. Median OS was 15.4 months (18.2 in BCLC-B vs 13.6 in BCLC-C). OS was not modified by comorbidities, age or period with more expertise.ConclusionsSorafenib appears to be safe in elderly patients with HCC. This is the first study to characterize the profile of elderly patients to be considered for systemic treatment. These findings could be used as the reference profile for elderly candidates for atezolizumab-bevacizumab.

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Efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma

Cited by 5 publications

References 32 publications

Deterioration of liver function and aging disturb sequential systemic therapy for unresectable hepatocellular carcinoma

Deterioration of liver function and aging disturb sequential systemic therapy for unresectable hepatocellular carcinoma

Efficacy and Safety of TKI Plus PD-1 Inhibitors in Elderly uHCC Patients: A Retrospective Study

Survival and adverse events of elderly patients treated with sorafenib for hepatocellular carcinoma

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