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. 2021 Jul;10(4):370-379.
doi: 10.1159/000515551. Epub 2021 Jun 15.

Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma

Francesco Tovoli  1 , Vincenzo Dadduzio  2 , Stefania De Lorenzo  3 , Lorenza Rimassa  4   5 , Gianluca Masi  6 , Massimo Iavarone  7 , Fabio Marra  8 , Ingrid Garajova  9 , Maria Pia Brizzi  10 , Bruno Daniele  11 , Franco Trevisani  12   13 , Carlo Messina  14 , Francesco Di Clemente  15 , Sara Pini  16 , Giuseppe Cabibbo  17 , Alessandro Granito  1   13 , Mario Domenico Rizzato  2   18 , Vittorina Zagonel  2 , Giovanni Brandi  3 , Tiziana Pressiani  5 , Piera Federico  11 , Caterina Vivaldi  6 , Irene Bergna  7 , Claudia Campani  8 , Fabio Piscaglia  1   13
Affiliations

Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma

Francesco Tovoli et al. Liver Cancer. 2021 Jul.

Abstract

Introduction: Cabozantinib has been approved by the European Medicine Agency (EMA) for hepatocellular carcinoma (HCC) previously treated with sorafenib. Cabozantinib is also being tested in combination with immune checkpoint inhibitors in the frontline setting. Real-life clinical data of cabozantinib for HCC are still lacking. Moreover, the prognostic factors for HCC treated with cabozantinib have not been investigated.

Methods: We evaluated clinical data and outcome of HCC patients who received cabozantinib in the legal context of named patient use in Italy.

Results: Ninety-six patients from 15 centres received cabozantinib. All patients had preserved liver function (Child-Pugh A), mostly with an advanced HCC (77.1%) in a third-line setting (75.0%). The prevalence of performance status (PS) > 0, macrovascular invasion (MVI), extrahepatic spread, and alpha-fetoprotein (AFP) >400 ng/mL was 50.0, 30.2, 67.7, and 44.8%, respectively. Median overall survival (OS) and progression-free survival were 12.1 (95% confidence interval 9.4-14.8) and 5.1 (3.3-6.9) months, respectively. Most common treatment-related adverse events (AEs) were fatigue (67.7%), diarrhoea (54.2%), anorexia (45.8%), HFSR (43.8%), weight loss (24.0%), and hypertension (24.0%). Most common treatment-related Grade 3-4 AEs were fatigue (6.3%), HFSR (6.3%), and increased aminotransferases (6.3%). MVI, ECOG-PS > 0, and AFP >400 ng/mL predicted a worse OS. Discontinuation for intolerance and no new extrahepatic lesions at the progression were associated with better outcomes.

Conclusions: In a real-life Western scenario (mostly in a third-line setting), cabozantinib efficacy and safety data were comparable with those reported in its registration trial. Data regarding the prognostic factors might help in patient selection and design of clinical trials.

Keywords: Cabozantinib; Hepatocellular carcinoma; Outcome; Sorafenib; Tyrosine kinase inhibitors.

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Conflict of interest statement

F.To.: consultant for Bayer; advisory board for Guerbet. V.D.: personal fees from Bayer, MSD, Eisai, and Ipsen. L.R.: consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Celgene, Eisai, Exelixis, Hengrui, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi; lectures fees from AbbVie, Amgen, Eisai, Gilead, Incyte, Ipsen, Lilly, Roche, Sanofi; travel fees from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, and Roche. M.I.: speaking and teaching for Bayer, Gilead Science, Janssen, BTG, AbbVie; consultant for BCG; Editorial Board Member of Liver Cancer. F.M.: consultant for Bayer and Ipsen, travel grants from Bayer. B.D.: honoraria from Ipsen, AstraZeneca, Incyte, Lilly, Eisai, Bayer, Roche, and MSD. F.Tr.: advisory board for Bayer, Alfasigma, Bristol-Myers Squibb, and Sirtex. G.C.: advisory board for Bayer; V.Z.: advisory board for Bristol-Myers Squibb and Merck; speakers' bureau for AstraZeneca and Lilly; personal fees from Bayer, Roche, and Servier. G.B.: advisory board for Eli Lilly and MSD. T.P. institutional research funding from Eli Lilly. F.P.: consultant for Astrazeneca, Bayer AG, EISAI, GE, and Tiziana life sciences; speaker's bureau honoraria from Bayer AG, Bracco, EISAI, and Laforce; and research contract with Esaote; Massimo Iavarone and Fabio Piscaglia are Editorial Board Members of Liver Cancer. The remaining authors declared no conflict of interests.

Figures

Fig. 1
Fig. 1
OS in the study population. OS, overall survival; CI, confidence interval.
Fig. 2
Fig. 2
PFS in the study population. PFS, progression-free survival; CI, confidence interval.
Fig. 3
Fig. 3
Best radiological response according to the RECIST 1.1 in our study population. PD, progressive disease; SD, stable disease; PR, partial response; RECIST 1.1, Response Evaluation Criteria in Solid Tumours version 1.1.
Fig. 4
Fig. 4
Overview of the therapeutic sequences of systemic drugs for HCC in our study population (n = 96).
See this image and copyright information in PMC

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