4688 - Prognostic and predictive factors from the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (aHCC)

Background

C improved overall survival (OS) and progression-free survival (PFS) vs P in the phase 3 CELESTIAL trial (NCT01908426). Median OS was 10.2 mo with C vs 8.0 mo with P (HR 0.76, 95% CI 0.63–0.92; p = 0.005), and median PFS was 5.2 mo vs 1.9 mo (HR 0.44, 95% CI 0.36–0.52; p < 0.001) (Abou-Alfa, NEJM 2018). Here, retrospective univariate (UV) and multivariate (MV) analyses were done to identify prognostic and predictive factors for OS from CELESTIAL.

Methods

707 patients (pts) were randomized 2:1 to receive C (60 mg qd) or P. Pts were Child-Pugh grade A and ECOG PS ≤ 1 and must have received prior sorafenib and could have received up to 2 prior lines of systemic therapy for HCC. UV and MV analyses of OS were done using the Cox proportional hazard regression model to compare subgroups defined by baseline variables within each treatment group (Bruix, J Hepatol 2017). MV analyses used backward selection with cutoffs of p ≤ 0.1 for inclusion and p ≤ 0.05 for retention of prognostic factors in the final model. Variables with p ≤ 0.05 for treatment-subgroup interaction were considered possible predictive factors for treatment benefit.

Results

Age, sex, race, region, and etiology were not significant covariates in stepwise UV and MV analyses of OS. Nine baseline variables related to disease status, laboratory values, or prior therapy were identified as possible prognostic factors for OS in one or both treatment groups (Table). No covariates were found to be predictive of an OS benefit with C.Table:

749P

Conclusions

Exploratory UV and MV analyses identified high baseline values of AFP, alkaline phosphatase, ALBI grade, neutrophil to lymphocyte ratio, and number of disease sites as possible prognostic factors for shorter OS in previously treated aHCC. Disease etiology and demographic factors such as race and region were not found to be prognostic for OS.

Clinical trial identification

NCT01908426.

Editorial acknowledgement

David Markby, Exelixis Inc.

Legal entity responsible for the study

Exelixis Inc.

Funding

Exelixis Inc.

Disclosure

T. Meyer: Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): BTG; Research grant / Funding (institution): Ipsen. R.K. Kelley: Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution), Inst.: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Inst.: Agios; Advisory / Consultancy, Research grant / Funding (institution), Inst.: BMS; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): QED; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Taiho. M. Mangeshkar: Shareholder / Stockholder / Stock options, Full / Part-time employment: Exelixis Inc. A. Cheng: Honoraria (self): Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Honoraria (self): Merck Sharp Dohme; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ono Pharmaceuticals; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: IQVIA; Advisory / Consultancy: Bayer Schering Pharma; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Nucleix Ltd; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer Yakuhin, Ltd; Speaker Bureau / Expert testimony: Amgen Taiwan. A.B. El-Khoueiry: Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: EMD Serono; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self): Novartis; Honoraria (self), Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: CytomX Therapeutics; Research grant / Funding (self): Astex Pharmaceuticals. G.K. Abou-Alfa: Advisory / Consultancy: 3DMedcare; Advisory / Consultancy, Research grant / Funding (institution): Agios; Research grant / Funding (institution): ActaBiologica; Advisory / Consultancy: Alignmed; Advisory / Consultancy: Amgen; Advisory / Consultancy: Antengene; Advisory / Consultancy: Aptus; Advisory / Consultancy: Aslan; Research grant / Funding (institution): Array; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Beigene; Advisory / Consultancy: Bioline; Advisory / Consultancy: BMS; Advisory / Consultancy: Boston Scientific; Advisory / Consultancy: Bridgebio; Advisory / Consultancy: Carsgen; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy, Research grant / Funding (institution): Casi; Advisory / Consultancy: Cipla; Advisory / Consultancy: CytomX; Advisory / Consultancy: Daiichi; Advisory / Consultancy: Debio; Advisory / Consultancy: Delcath; Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy: Genoscience; Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Halozyme; Advisory / Consultancy: Hengrui; Advisory / Consultancy, Research grant / Funding (institution): Incyte; Advisory / Consultancy: Inovio; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Jazz; Advisory / Consultancy: Jansen; Advisory / Consultancy: Kyowa Kirin; Advisory / Consultancy: LAM; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy: Loxo; Research grant / Funding (institution): Mabvax; Advisory / Consultancy: Merck; Advisory / Consultancy: Mina; Research grant / Funding (institution): Novartis; Advisory / Consultancy: Novella; Research grant / Funding (institution): OncoQuest; Advisory / Consultancy: Onxeo; Advisory / Consultancy: PCI Biotech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Pieris; Research grant / Funding (institution): Polaris Puma; Advisory / Consultancy, Research grant / Funding (institution): QED; Advisory / Consultancy: Redhill; Research grant / Funding (institution): Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: Silenseed; Advisory / Consultancy: Sillajen; Advisory / Consultancy: Sobi; Advisory / Consultancy: Targovax; Advisory / Consultancy: Tekmira; Advisory / Consultancy: Twoxa; Advisory / Consultancy: Vicus; Advisory / Consultancy: Yakult; Advisory / Consultancy: Yiviva.