Lenvatinib May Drastically Change the Treatment Landscape of Hepatocellular Carcinoma

Kudo, Masatoshi

doi:10.1159/000487148

Cited by 104 publications

(106 citation statements)

References 58 publications

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“…In the nonsurgical setting, pre‐intervention AFP levels have been shown to predict survival prognosis with locoregional therapies as well as with sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab . Two studies evaluating radiofrequency ablation (RFA) for first‐line treatment of HCC in patients with Child‐Pugh A/B cirrhosis demonstrated 5‐year OS rates of 68% to 76% .…”

Section: Clinical Relevance Of Afp In Hccmentioning

confidence: 99%

Biology and significance of alpha‐fetoprotein in hepatocellular carcinoma

Galle

Foerster

Kudo

et al. 2019

Liver International

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390

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Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths globally due, in part, to the majority of patients being diagnosed with intermediate or advanced stage disease. Our increased understanding of the heterogeneous molecular pathogenesis of HCC has led to significant developments in novel targeted therapies. Despite these advances, there remains a high unmet need for new treatment options. HCC is a complex disease with multiple pathogenic mechanisms caused by a variety of risk factors, making it difficult to characterize with a single biomarker.In fact, numerous biomarkers have been studied in HCC, but alpha-fetoprotein (AFP) remains the most widely used and accepted serum marker since its discovery over 60 years ago. This review summarizes the most relevant studies associated with the regulation of AFP at the gene and protein levels; the pathophysiology of AFP as a pro-proliferative protein; and the correlation of AFP with molecular HCC subclasses, the vascular endothelial growth factor pathway and angiogenesis. Also described are | 2215 GALLE Et AL.

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Section: Clinical Relevance Of Afp In Hccmentioning

confidence: 99%

Biology and significance of alpha‐fetoprotein in hepatocellular carcinoma

Galle

Foerster

Kudo

et al. 2019

Liver International

Self Cite

390

284

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“…The observed adverse events, including thrombocytopenia and proteinuria, were well controlled, and long‐term lenvatinib treatment was achieved with no deterioration of PS. Lenvatinib has been reported to inhibit VEGF1–3, FGFR1–4, platelet‐derived growth factor receptor‐α, RET, and KIT, showing both anti‐angiogenic and direct antitumor activities . In this case, the vascularity of the intrahepatic hypervascular nodule was lost in the early phase of dynamic CT, soon after treatment with lenvatinib.…”

Section: Discussionmentioning

confidence: 80%

“…In a multicenter, randomized, open‐label, phase III trial (REFLECT), lenvatinib was compared with sorafenib and showed the treatment effect on OS by statistical confirmation of non‐inferiority . This novel anti‐angiogenesis multikinase inhibitor is thus now expected to be introduced into clinical practice as a first‐line systemic chemotherapy for advanced HCC, along with sorafenib …”

Section: Introductionmentioning

confidence: 99%

Long‐term antitumor effect of lenvatinib on unresectable hepatocellular carcinoma with portal vein invasion

Takeda

Nishijima

Nasu

et al. 2019

Hepatology Research

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Lenvatinib is a novel multikinase inhibitor that has recently shown antitumor activity against hepatocellular carcinoma (HCC) in a phase III trial. We report the case of a woman in whom lenvatinib showed long‐term antitumor activity, and in whom computed tomography (CT) scans revealed a series of suggestive radiological changes on the intratumor vascularity. A 68‐year‐old woman with hepatitis C virus‐related liver disease presented with multiple HCCs. Following previous therapy, including six sessions of transcatheter arterial chemoembolization, we introduced lenvatinib monotherapy. Lenvatinib could rapidly cause hypovascularity in the main hypervascular target lesion, and portal vein tumor thrombosis also became undetectable 11 months after the initiation of lenvatinib. These radiological changes suggested that lenvatinib could exert not only anti‐angiogenic activity but also direct antitumoral effect. Of note, CT scans during lenvatinib treatment revealed the target lesion as a low‐density area in the early arterial phase, whereas scans during drug interruption due to proteinuria showed that the lesion was enhanced in the arterial phase. Finally, near‐complete response could be achieved as the best response. We successfully managed various adverse events including proteinuria and hypertension, and the patient was able to continue this lenvatinib therapy for more than 4 years with well‐controlled general condition. We report the first case of a patient with HCC in whom lenvatinib monotherapy demonstrated long‐term antitumor activity. Suggestive radiological changes reflecting intratumor vascularity as presented here should be considered in patients receiving lenvatinib for HCC.

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“…Survival bene ts of sorafenib are limited, and some HCC patients later succumbed to diseaseprogression after responding initially to sorafenib [38,39].It is noteworthy in particular, that as HCC is a highly heterogeneous malignancy, different individuals suffering from it might show variable responses to sorafenib thus resulting in an increasedneed for biomarkers regarding the selection of patients as well as prediction of response.Recently, the understanding of the underlying mechanism that in uencesthe responses of HCC towards sorafenib has increased [37].Llovetet algenerated a newly 146-gene signature able to recognize 30% of patients who bene tted from sorafenib [4]. A recent study reportedFLT3 may be able to predict sorafenib bene t in HCC patients.Numerous other works have reported that amplifying VEGFA, FGF3/FGF4 or FGF19 may potentially predict HCC responseto sorafenib [40,41].However, for sorafenib, no effective biomarkers of response have been identi ed [4].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Nomogram for Sorafenib Benefit in Hepatitis B Virus related Hepatocellular Carcinoma after Partial Hepatectomy

Dong

Yan

Huang

et al. 2020

Preprint

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Background The prediction regarding the long-term prognosis of individuals subjected to sorafenib treatment following partial hepatectomy due to hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) is rather difficult.The objective behind this work is to create an effective prognostic nomogram of sorafenib for personalized therapy of HBV-relatedHCC. Methods 234 HBV-related HCC patients subjected or not subjected to sorafenibtreatment following partial hepatectomy at the Eastern Hepatobiliary Surgery Hospital from 2008 to 2013 were compared to investigate the association between index levels and sorafenib benefit. The optimal cut-off point of the overall survival (OS) factor level was determined by x-tile.The selection of indicators is based on clinical findings. The Cox regression model with an interaction term was employed for evaluating the predictive value. Using a multivariate Cox proportional hazards model a Nomogram was subsequently formulated to analyze 113 patients treated with sorafenib. Determination of nomogram’s discriminative ability and predictive accuracy was done using the concordance index (C-index), calibration, and ROC curve. Results Subgroup analysis revealed that Low GPC3,pERK, pAKT, serum AFP levels, without MVI, under 50 years old, male, TNM stage I/II and BCLC stage 0/A wereassociated significantly with a better OS in patients subjected to sorafenib treatment compared to those not treated with sorafenib after surgery. The independent factors for OS were found be GPC3, pERK, pAKT, serum AST and BCLC stage, following multivariate analysis of the sorafenib cohort, which was all included in the nomogram. The survival probability based on the calibration curve shows that the prediction of the nomogram was in good agreement with the actual observation. Survival was predicted to be 0.73(95% CI, 0.67 to 0.78) based on the C-index of the nomogram. The area under the ROC curve (AUC) for the nomogram to predict the survival for 1, 3, and 5-year was 0.726, 0.816, and 0.823, respectively. Conclusion This proposed nomogram has the potential to make quite a precise prediction regarding the prognosis of HBV-related HCC patients,who underwent sorafenib therapy following partial hepatectomy.

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Lenvatinib May Drastically Change the Treatment Landscape of Hepatocellular Carcinoma

Cited by 104 publications

References 58 publications

Biology and significance of alpha‐fetoprotein in hepatocellular carcinoma

Biology and significance of alpha‐fetoprotein in hepatocellular carcinoma

Long‐term antitumor effect of lenvatinib on unresectable hepatocellular carcinoma with portal vein invasion

Prognostic Nomogram for Sorafenib Benefit in Hepatitis B Virus related Hepatocellular Carcinoma after Partial Hepatectomy

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