Safety and efficacy of cabozantinib for patients with advanced hepatocellular carcinoma who advanced to Child-Pugh B liver function at study week 8: a retrospective analysis of the CELESTIAL randomised controlled trial

Anthony B El-Khoueiry, Tim Meyer, Ann-Lii Cheng, Lorenza Rimassa, Suvajit Sen, Steven Milwee, Robin Kate Kelley, Ghassan K Abou-Alfa, Anthony B El-Khoueiry, Tim Meyer, Ann-Lii Cheng, Lorenza Rimassa, Suvajit Sen, Steven Milwee, Robin Kate Kelley, Ghassan K Abou-Alfa

Abstract

Background: Patients with hepatocellular carcinoma (HCC) and Child-Pugh B liver cirrhosis have poor prognosis and are underrepresented in clinical trials. The CELESTIAL trial, in which cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with HCC and Child-Pugh A liver cirrhosis at baseline, was evaluated for outcomes in patients who had Child-Pugh B cirrhosis at Week 8.

Methods: This was a retrospective analysis of adult patients with previously treated advanced HCC. Child-Pugh B status was assessed by the investigator. Patients were randomised 2:1 to cabozantinib (60 mg once daily) or placebo.

Results: Fifty-one patients receiving cabozantinib and 22 receiving placebo had Child-Pugh B cirrhosis at Week 8. Safety and tolerability of cabozantinib for the Child-Pugh B subgroup were consistent with the overall population. For cabozantinib- versus placebo-treated patients, median OS from randomisation was 8.5 versus 3.8 months (HR 0.32, 95% CI 0.18-0.58), median PFS was 3.7 versus 1.9 months (HR 0.44, 95% CI 0.25-0.76), and best response was stable disease in 57% versus 23% of patients.

Conclusions: These encouraging results with cabozantinib support the initiation of prospective studies in patients with advanced HCC and Child-Pugh B liver function.

Clinical trial registration: NCT01908426.

Keywords: Cabozantinib; Child–Pugh B; Hepatocellular carcinoma.

Conflict of interest statement

ABEK: Consulting/advisory: AstraZeneca, Bayer, BMS, Celgene, CytomX, Eisai, Exelixis, Novartis, Roche; grant support: AstraZeneca, Astex; speakers’ bureau fee: Merrimack.

TM: Grant support/consulting: Bayer, BMS, BTG, Eisai, Merck.

ALC: Honorarium: Bayer, Eisai, Merck, Merck Serono, Novartis, Ono Pharma., Roche, IQVIA; consulting/advisory: Bayer, BMS, Eisai, Exelixis, IQVIA, Merck Serono, Novartis, Nucleix, Ono Pharma., Roche; speaker bureau fees: Amgen, Bayer, Novartis, Eisai, Ono Pharma. Yakuhin.

LR: Consulting/advisory: Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Zymeworks; speakers bureau fee: AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi; travel fee: Ipsen; research funding: Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks.

SS, SM: Employees of Exelixis.

RKK: Consulting/advisory: Agios, AstraZeneca, BMS, Exact Sciences, Genentech/Roche, Gilead, Ipsen, Merck; research funding: Adaptimmune, Agios, AstraZeneca, Bayer, BMS, Celgene, Eli Lily, EMD Serono, Exelixis, MedImmune, Merck, Novartis, Partner Therapeutics, Taiho Pharmaceuticals.

GKAA: Grant support: ActaBiologica, Agios, AstraZeneca, Bayer, Beigene, Berry Genomics, BMS, Casi, Celgene, Exelixis, Genentech/Roche, Halozyme, Incyte, Mabvax, Puma, QED, Sillajen, Yiviva; consulting/advisory: Agios, AstraZeneca, Autem, Bayer, Beigene, Berry Genomics, Celgene, CytomX, Debio, Eisai, Eli Lilly, Flatiron, Genentech/Roche, Gilead, Incyte, Ipsen, LAM, Loxo, Merck, MINA, Polaris, QED, Redhill, Silenseed, Sillajen, Sobi, Therabionics, Twoxar, Vector, Yiviva.

© 2022. The Author(s).

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/8994237/bin/12885_2022_9453_Fig1_HTML.jpg
Fig 1 Overall survival and progression-free survival in the Child–Pugh B subgroup. CI, confidence interval; mo, months; no, number; OS overall survival, PFS, progression-free survival

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