Lenvatinib in Advanced Hepatocellular Carcinoma

Kudo, Masatoshi

doi:10.1159/000479573

Cited by 45 publications

(50 citation statements)

References 23 publications

(26 reference statements)

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“…Kaplan-Meier plots showed a reduction in the time to dose reduction or withdrawal with increasing AUC [36,37]. A similar relationship was observed between body weight and time to dose reduction or withdrawal; time to dose reduction or withdrawal became shorter as body weight decreased, demonstrating that dose reduction or withdrawal may be required earlier in lighter patients than in heavier patients [36,37].…”

Section: Relationship Between Pharmacokinetics Of Lenvatinib and Dosesupporting

confidence: 59%

“…Close examination of the patients' background suggested that body weight and serum lenvatinib levels were associated with dose reduction or early treatment withdrawal. More precisely, patients who had dose reduction or early withdrawal within 30 days of lenvatinib treatment were significantly lighter (median weight, 54.1 vs. 67.6 kg) and had a significantly higher minimum plasma concentration of lenvatinib (trough concentration [C1D15C trough ], 62.4 vs. 33.9 ng/mL) [36,37].…”

Section: Significance Of Body Weight-based Dosingmentioning

confidence: 99%

“…A relationship was observed between body weight and plasma lenvatinib level (represented by the area under the blood concentration time curve [AUC]), indicating that exposure to lenvatinib increased as body weight decreased [36,37]. This trend was more prominent in HCC patients than in patients with other types of solid cancers, suggesting that the relationship has an especially strong impact in HCC patients.…”

Section: Relationship Between Body Weight and Plasma Level Of Lenvatimentioning

confidence: 99%

“…The sensitivity and specificity of different body weight cutoff values for predicting the early occurrence (within 30 days after the start of therapy) of dose reduction and withdrawal were calculated to draw receiver operating characteristic (ROC) curves [36,37]. The optimal body weight cutoff (the point at which the distance between the top left corner of the graph and the ROC is smallest) that most effectively distinguished the high-risk group for early withdrawal or dose reduction of lenvatinib was 57.8 kg, showing a sensitivity of 0.77 and specificity of 0.67 (false-positive rate, 0.33).…”

Section: Optimal Cutoff Values For Body Weight and Auc In Hcc Patientmentioning

confidence: 99%

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Lenvatinib May Drastically Change the Treatment Landscape of Hepatocellular Carcinoma

Kudo

2018

Liver Cancer

Self Cite

109

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Section: Relationship Between Pharmacokinetics Of Lenvatinib and Dosesupporting

confidence: 59%

Section: Significance Of Body Weight-based Dosingmentioning

confidence: 99%

Section: Relationship Between Body Weight and Plasma Level Of Lenvatimentioning

confidence: 99%

Section: Optimal Cutoff Values For Body Weight and Auc In Hcc Patientmentioning

confidence: 99%

See 2 more Smart Citations

Lenvatinib May Drastically Change the Treatment Landscape of Hepatocellular Carcinoma

Kudo

2018

Liver Cancer

Self Cite

109

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“…The median OS time for lenvatinib of 13.6 months was noninferior to that of sorafenib (12.3 months), reaching its primary endpoint of noninferiority [8]. As a result, lenvatinib [9-11] was approved for first-line treatment of unresectable HCC by the Japanese Pharmaceuticals and Medical Devices Agency in March 2018, by the FDA in August 2018, and by the EMA right after (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Implications of Immunotherapy in Hepatobiliary Tumors

2019

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Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related death worldwide. Upon ineligibility for resection, liver transplantation, or locoregional therapies, sorafenib has been the only systemic treatment option of advanced HCC for more than a decade. Immunotherapy is an evolving HCC treatment option that has shown promise in treatment efficacy at an acceptable safety profile during several preceding phase I/II trials. Numerous clinical trials of immune checkpoint inhibitors (ICPIs) alone, in combination of two, or combined with other targeted or locoregional therapies are ongoing. Encouraging results of two-phase III trials testing pembrolizumab or nivolumab versus standard care therapy even resulted in Food and Drug Administration approval for second-line treatment of advanced HCC. ICPIs may open new avenues to the treatment of hepatobiliary tumors, alone or in combination.

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Prognostic value of skeletal muscle mass during tyrosine kinase inhibitor (TKI) therapy in cancer patients: a systematic review and meta-analysis

et al. 2020

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Low muscle mass has been associated with worse clinical outcomes in various cancers. This work investigated whether, during tyrosine kinases inhibitors (TKIs) therapy, low muscle mass was associated with treatment toxicity and survival outcomes. A systematic literature search was performed in Pubmed, Web of Science, and Scopus databases from inception to June 2020, based on fixed inclusion and exclusion criteria. Effect sizes were estimated with hazard ratios (HR) and odds ratios (OR) with 95% confidence interval (CI) and heterogeneity was assessed by measuring inconsistency (I2) based on the Chi squared test. A total of 24 retrospective studies were identified, enrolling patients treated with sorafenib (n = 12), sunitinib (n = 6), lenvatinib (n = 3), regorafenib (n = 2), gefitinib (n = 1), imatinib (n = 1), and pazopanib (n = 1). Thirteen studies were deemed eligible for pooled analyses. Meta-analyses found a significant effect of low muscle mass on dose-limiting toxicity (DLT) (OR 2.40, 95% CI 1.26–4.58, p = 0.008, I2 = 51%) in patients treated with TKI therapy. A subgroup analysis by treatment showed an association between DLT and low muscle during sorafenib or sunitinib, although not significant. A significant association between low skeletal muscle index and poorer overall survival was observed in HCC patients treated with sorafenib (HR 1.45, 95% CI 1.07–1.96, p = 0.02). For other TKIs, although some results showed an association between low muscle mass and worse outcomes, the number of studies for each TKI therapy was too small to reach conclusions. Skeletal muscle mass could influence the prognosis of some TKI-treated patients. This effect is demonstrated in sorafenib-treated HCC patients but remains almost unexplored in other cancer patients undergoing TKI therapy. Further prospective studies with large sample size and sufficient follow-up are needed to clarify the role of muscle mass in the metabolism of TKI-based cancer treatment, and its association with toxicity and survival.

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Lenvatinib in Advanced Hepatocellular Carcinoma

Cited by 45 publications

References 23 publications

Lenvatinib May Drastically Change the Treatment Landscape of Hepatocellular Carcinoma

Lenvatinib May Drastically Change the Treatment Landscape of Hepatocellular Carcinoma

Implications of Immunotherapy in Hepatobiliary Tumors

Prognostic value of skeletal muscle mass during tyrosine kinase inhibitor (TKI) therapy in cancer patients: a systematic review and meta-analysis

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