Abstract 4688
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
MV analysis of OS | Cabozantinib | Placebo | ||
---|---|---|---|---|
p-value | HR | p-value | HR | |
ECOG PS [≥1 vs 0] | 0.0020 | 1.43 | 0.96 | 1.01 |
Macrovascular invasion (MVI) [yes vs no] | 0.0023 | 1.47 | 0.16 | 1.28 |
Number of sites [2 vs 1] | 0.047 | 1.33 | 0.0024 | 1.84 |
Number of sites [3 vs 1] | <0.0001 | 1.82 | 0.010 | 1.70 |
Alpha-fetoprotein (AFP) [≥400 vs < 400 ng/mL] | <0.0001 | 1.72 | <0.0001 | 1.95 |
Albumin-bilirubin (ALBI) grade [≥2 vs 1] | 0.0005 | 1.57 | 0.022 | 1.48 |
Neutrophil to lymphocyte ratio [≥median vs 0.012 | 1.34 | 0.025 | 1.45 | |
Alkaline phosphatase [≥median vs 0.0009 | 1.50 | <0.0001 | 2.15 | |
Prior transarterial chemoembolization (TACE) [yes vs no] | 0.34 | 0.90 | 0.028 | 0.69 |
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.
Resources from the same session
3608 - Prognostic impact of Body Mass Index (BMI) on overall survival in patients with metastatic breast cancer
Presenter: Khalil SALEH
Session: Poster Display session 2
Resources:
Abstract
2686 - Clinicopathological characteristics, survival and prognostic factors of breast cancer-related microangiopathic haemolytic anemia: a multicenter study
Presenter: Marion Alhenc Gelas
Session: Poster Display session 2
Resources:
Abstract
1565 - Metabolic tumor volume by 18F-FDG PET/CT is an independent prognostic factor in metastatic breast cancer
Presenter: Heekyung Ahn
Session: Poster Display session 2
Resources:
Abstract
4498 - Patient Preferences for breast cancer treatments: A Discrete Choice Experiment from four European countries
Presenter: Thomais Konstantopoulou
Session: Poster Display session 2
Resources:
Abstract
1423 - Palbociclib plus fulvestrant as second- or later-line therapy for patients with locally advanced, inoperable or metastatic HR+/HER2- breast cancer in Germany: Interim results of the INGE-B phase 2 study
Presenter: Diana Lüftner
Session: Poster Display session 2
Resources:
Abstract
2284 - Ventriculoperitoneal Shunt for CNS Metastasis in Breast Cancer: Clinical Outcomes Based on Intrinsic Subtype
Presenter: Hee Kyung Kim
Session: Poster Display session 2
Resources:
Abstract
4598 - Administration of chemotherapy for metastatic breast cancer near the end of life: a population registry study
Presenter: Luisa Edman Kessler
Session: Poster Display session 2
Resources:
Abstract
5706 - Prognostic value of histological growth pattern in patients operated for breast cancer liver metastases
Presenter: Ali Bohlok
Session: Poster Display session 2
Resources:
Abstract
1697 - Illness perceptions, quality of life and mood in metastatic breast cancer patients
Presenter: Isabel Domingues
Session: Poster Display session 2
Resources:
Abstract
1935 - Multidisciplinary Treatments Increases Overall Survival in Patients with Newly Diagnosed Stage IV Breast Cancer:An Analysis of 2010–2014 SEER Data
Presenter: Jian Zhang
Session: Poster Display session 2
Resources:
Abstract