Efficacy and safety of cabozantinib for patients with advanced hepatocellular carcinoma based on albumin-bilirubin grade

Robin Kate Kelley, Rebecca Miksad, Irfan Cicin, YenHsun Chen, Heinz-Josef Klümpen, Stefano Kim, Zhong-Zhe Lin, Jillian Youkstetter, Saswati Hazra, Suvajit Sen, Ann-Lii Cheng, Anthony B El-Khoueiry, Tim Meyer, Ghassan K Abou-Alfa, Robin Kate Kelley, Rebecca Miksad, Irfan Cicin, YenHsun Chen, Heinz-Josef Klümpen, Stefano Kim, Zhong-Zhe Lin, Jillian Youkstetter, Saswati Hazra, Suvajit Sen, Ann-Lii Cheng, Anthony B El-Khoueiry, Tim Meyer, Ghassan K Abou-Alfa

Abstract

Background: Albumin-bilirubin (ALBI) grade is an objective measure of liver function for patients with hepatocellular carcinoma (HCC). The tyrosine kinase inhibitor cabozantinib is approved for patients with advanced HCC who have received prior sorafenib based on the phase 3 CELESTIAL trial (NCT01908426). Cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated HCC.

Methods: Patients were randomised 2:1 to receive cabozantinib 60 mg or placebo orally every day. Clinical outcomes in patients with ALBI grade 1 or 2 at baseline were evaluated in CELESTIAL. ALBI scores were retrospectively calculated based on baseline serum albumin and total bilirubin, with an ALBI grade of 1 defined as ≤ -2.60 score and a grade of 2 as a score of > -2.60 to ≤ -1.39.

Results: Cabozantinib improved OS and PFS versus placebo in both ALBI grade 1 (hazard ratio [HR] [95% CI]: 0.63 [0.46-0.86] and 0.42 [0.32-0.56]) and ALBI grade 2 (HR [95% CI]: 0.84 [0.66-1.06] and 0.46 [0.37-0.58]) subgroups. Adverse events were consistent with those in the overall population. Rates of grade 3/4 adverse events associated with hepatic decompensation were generally low and were more common among patients in the ALBI grade 2 subgroup.

Discussion: These results provide initial support of cabozantinib in patients with advanced HCC irrespective of ALBI grade 1 or 2.

Trial registration number: ClinicalTrials.gov number, NCT01908426.

Conflict of interest statement

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. RM: Employee of Flatiron Health, equity ownership Flatiron Health, stock ownership Roche. Consulting: De Luca Foundation. IC: Consulting/advisory: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Quintiles; research funding: Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Merck, Merck Serono, Parexel, Pfizer, Quintiles, Taiho. YC, ZZL: Nothing to report. HJK: Consulting/advisory: Ipsen; research funding: Bayer, BTG, Daichii, Exelixis, Ipsen, ITM, Novartis, Sirtex, Taiho. SK: Honorarium: Bayer, Boehringer, Ipsen, MSD, Sanofi, Servier; research funding: Pfizer, Roche, Sanofi. JY, SH, SS: Employees of Exelixis. 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. 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. 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.

© 2021. The Author(s).

Figures

Fig. 1. Overall survival by ALBI grade.
Fig. 1. Overall survival by ALBI grade.
Hazard ratios are unstratified. ALBI albumin–bilirubin, CI confidence interval, OS overall survival.
Fig. 2. Progression-free survival by ALBI grade.
Fig. 2. Progression-free survival by ALBI grade.
Hazard ratios are unstratified. ALBI, albumin–bilirubin, CI confidence interval, PFS progression-free survival.

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