Abstract 127P
Background
ALBI grade is an objective measure of liver function for patients with HCC; higher ALBI grade is associated with worse prognosis. In the phase 3 CELESTIAL trial (NCT01908426), cabozantinib, an inhibitor of MET, VEGFR, and AXL, significantly improved overall survival (OS) and progression-free survival (PFS) vs placebo in patients with previously treated HCC and is now approved for patients with HCC who received prior sorafenib. Here, we evaluate outcomes based on ALBI grade in the CELESTIAL trial.
Methods
707 patients were randomized 2:1 to cabozantinib (60 mg daily) or placebo. Eligible patients had HCC, Child-Pugh score A, and ECOG PS ≤ 1. Patients received prior sorafenib and ≤2 lines of prior systemic therapy for HCC. Baseline ALBI score was calculated from serum albumin and total bilirubin measured centrally, and was used to determine ALBI grade (Johnson, J Clin Oncol. 2015;33:550-8).
Results
At baseline, 186 patients (40%) were ALBI grade 1 and 282 (60%) were ALBI grade 2 in the cabozantinib arm; 182 patients (43%) were ALBI grade 1 and 133 (56%) were ALBI grade 2 in the placebo arm. Two patients in each arm were ALBI grade 3. Patients with ALBI grade 1 had better ECOG PS (61% ECOG 0 & 39% ECOG 1) vs those with ALBI grade 2 (48% ECOG 0 & 52% ECOG 1). In patients with ALBI grade 1, median OS was 17.5 months with cabozantinib vs 11.4 months with placebo (HR 0.63, 95% CI 0.46-0.86). In patients with ALBI grade 2, median OS was 8.0 months with cabozantinib vs 6.4 months with placebo (HR 0.84, 95% CI 0.66-1.06). In patients with ALBI grade 1, median PFS was 6.5 months with cabozantinib vs 1.9 months with placebo (HR 0.42, 95% CI 0.32-0.56) and in patients with ALBI grade 2, median PFS was 3.7 months with cabozantinib vs 1.9 months with placebo (HR 0.46, 95% CI 0.37-0.58). Common grade 3/4 adverse events in both groups were consistent with the overall population. Treatment related discontinuations in the cabozantinib arm were 12% and 19% for patients with ALBI grade 1 and 2.
Conclusions
Patients treated with cabozantinib had longer PFS and OS vs patients receiving placebo, regardless of ALBI grade. Outcomes were generally better in patients with ALBI grade 1 vs 2.
Clinical trial identification
NCT01908426 (Other Study ID Numbers: XL184-309).
Editorial acknowledgement
Suvajit Sen (Exelixis).
Legal entity responsible for the study
Exelixis.
Funding
Exelixis.
Disclosure
S.L. Chan: Advisory / Consultancy: Amgen. R. Miksad: Full / Part-time employment: Flatiron Health; Shareholder / Stockholder / Stock options: Flatiron Health; Research grant / Funding (institution): Exelixis, Bayer . I. Cicin: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Merck Sharp & Dohme Corp; Advisory / Consultancy: F. Hoffmann-La Roche; Advisory / Consultancy: Pfizer. H.J. Klumpen: Advisory / Consultancy: IPSEN; Research grant / Funding (institution), Local PI for clinical trial from the following organizations: IPSEN Exelexis, ITM, SIRTEX, Taiho, BAYER, DAICHII, Novartis, BTG . S. Kim: Research grant / Funding (institution): Genentech, Roche, Pfizer; Advisory / Consultancy: Amgen, Bayer, Boehringer Ingelheim, MSD, Novartis, Roche, Sanofi, Servier. J. Youkstetter: Shareholder / Stockholder / Stock options, Full / Part-time employment: Exelixis. S. Sen: Full / Part-time employment, Self and spouse: Exelixis; Shareholder / Stockholder / Stock options, Self and spouse: Exelixis. A-L. Cheng: Advisory / Consultancy: Bayer Schering Pharma; Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Ono Pharmaceutica; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Nucleix; Honoraria (self), Advisory / Consultancy: Roche/Genentech; Honoraria (self), Advisory / Consultancy: IQVIA; Honoraria (self): Merck Sharp Dohme. A.B. El-Khoueiry: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Astex; Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Agenus; Advisory / Consultancy: Merck; Advisory / Consultancy: EISAI; Advisory / Consultancy: Pieris; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Apeiron. T. Meyer: Advisory / Consultancy: BMS, BAYER, EISAI, BTG, AZ, BEIGENE, TARVEDA, MSD; Research grant / Funding (institution): BTG BAYER. R.K. Kelley: Advisory / Consultancy: Agios, AstraZeneca, Bayer, BMS (funding to institution) IDMC: Genentech/Roche (funding to self); Research grant / Funding (institution): Agios, AstraZeneca, Bayer, BMS, Eli Lilly, Exelixis, EMD Serono, Medimmune, Merck, Novartis, QED, Taiho. G.K. Abou-Alfa: Research grant / Funding (self): ActaBiologica,; Advisory / Consultancy, Research grant / Funding (self): Agios,; Research grant / Funding (self): Array,; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Bayer,; Advisory / Consultancy, Research grant / Funding (self): Beigene,; Advisory / Consultancy, Research grant / Funding (self): BMS,; Research grant / Funding (self): Casi,; Research grant / Funding (self): Celgene,; Research grant / Funding (self): Exelixis,; Research grant / Funding (self): Genentech,; Research grant / Funding (self): Halozyme,; Research grant / Funding (self): Incyte,; Research grant / Funding (self): Lilly,; Research grant / Funding (self): Mabvax,; Research grant / Funding (self): Novartis,; Research grant / Funding (self): OncoQuest,; Research grant / Funding (institution): Polaris Puma; Research grant / Funding (self): QED,; Research grant / Funding (self): Roche; Advisory / Consultancy: 3DMedcare,Agios, Alignmed, Amgen, Antengene, Aptus, Aslan, Astellas, AstraZeneca, Bayer, Beigene, Bioline, BMS, Boston Scientifc, Bridgebio, Carsgen, Celgene, Casi, Cipla, CytomX, Daiichi, Debio, Delcath, Eisai, Exelixis, Flatiron, Genoscience, Halozyme. All other authors have declared no conflicts of interest.
Resources from the same session
41P - Clinical verification on the relationship between serum lipid metabolism and the immune microenvironment in breast cancer patients
Presenter: Wataru Goto
Session: Poster display session
Resources:
Abstract
42P - Genome wide copy number analysis of circulating tumour cells in breast cancer liver metastasis
Presenter: Saber Imani
Session: Poster display session
Resources:
Abstract
43P - A hotspot variants p.H1047R and p.H1047L in p110α/ΔNp63α complex affects structure, function and contributes to susceptibility metastatic breast cancer
Presenter: Zou Linglin
Session: Poster display session
Resources:
Abstract
44P - Correlation of circulating tumour cells with PET-CT in metastatic breast cancer
Presenter: Venkata Pradeep Babu Koyyala
Session: Poster display session
Resources:
Abstract
45P - The challenge of evaluating new targeted therapies: Opportunities in stratifying the therapeutic response per tumour location
Presenter: Hubert Beaumont
Session: Poster display session
Resources:
Abstract
46P - Plasma soluble CD36 of breast cancer based on pathological and clinical characteristics
Presenter: Aditia Romadhoni
Session: Poster display session
Resources:
Abstract
47P - Investigation of the use of a novel S-1 administration method for treating metastatic and recurrent breast cancer
Presenter: MAYUKO MIKI
Session: Poster display session
Resources:
Abstract
48P - Development of MDA-MB-231-3D-Spheroid as a reliable model for studying Nav1.5 and nNav1.5-mediated breast cancer metastasis
Presenter: Ahmad Murtadha
Session: Poster display session
Resources:
Abstract
49P - Biochemical study on modifying role of variants of leptin gene and its receptor on serum leptin levels in breast cancer
Presenter: Alshimaa Alhanafy
Session: Poster display session
Resources:
Abstract
50P - Prognostic factors of recurrence or distant metastasis in elderly breast cancer patients
Presenter: Seungju Lee
Session: Poster display session
Resources:
Abstract