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
117P - Short-term and long-term outcomes of hepatectomy combined with intraoperative radiofrequency ablation for multiple colorectal liver metastases: A propensity score matching study
Presenter: Wenbai Huang
Session: Poster display session
Resources:
Abstract
119P - The impacts of dose-time-fractionation schedules on pathological complete response rate (pCR) and local recurrence (LR)
Presenter: Fu Jin
Session: Poster display session
Resources:
Abstract
120P - Platelet to lymphocyte ratio is associated with tumour localization and outcomes in patients with metastatic colorectal cancer
Presenter: Ahmet Bilici
Session: Poster display session
Resources:
Abstract
121P - Meta-analysis of three-dimensional versus two-dimensional laparoscopic surgery for rectal cancer
Presenter: Laiyuan Li
Session: Poster display session
Resources:
Abstract
128P - Tislelizumab in combination with chemotherapy for Chinese patients (Pts) with gastric/gastroesophageal junction cancer (GC/GEJC) or esophageal squamous cell carcinoma (ESCC)
Presenter: Yuxian Bai
Session: Poster display session
Resources:
Abstract
129P - Monitoring patient-specific mutation in ctDNA and CTC for tumour response evaluation after neoadjuvant chemotherapy in advanced gastric adenocarcinoma (NCT03425058)
Presenter: Tao Fu
Session: Poster display session
Resources:
Abstract
130P - Development of a liver cancer risk prediction model for the general population in china: A potential tool for screening
Presenter: Xiaoshuang Feng
Session: Poster display session
Resources:
Abstract
131P - Cabozantinib in Asian patients with hepatocellular carcinoma and other solid tumours: Population pharmacokinetics analysis
Presenter: Chih-Hung Hsu
Session: Poster display session
Resources:
Abstract
132P - Liposomal irinotecan (nal-IRI) plus 5-fluorouracil/levoleucovorin (5 FU/LV) vs 5-FU/LV in Japanese patients (pts) with gemcitabine-refractory metastatic pancreatic cancer (mPAC)
Presenter: Tatsuya Ioka
Session: Poster display session
Resources:
Abstract
133P - Prognostic and predictive factors from the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (aHCC)
Presenter: Thomas Yau
Session: Poster display session
Resources:
Abstract