Abstract 133P
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.
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.Table:
133P
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 |
Clinical trial identification
NCT01908426 (Other Study ID Numbers: XL184-309).
Editorial acknowledgement
David Markby (Exelixis).
Legal entity responsible for the study
Exelixis.
Funding
Exelixis.
Disclosure
T. Yau: Advisory / Consultancy: Exelixis; Honoraria (self): Ipen, Exelixis. T. Meyer: Advisory / Consultancy: BMS, BAYER, EISAI, BTG, AZ, BEIGENE, TARVEDA, MSD; Research grant / Funding (self): BTG BAYER. R.K. Kelley: Research grant / Funding (institution), Funding to institution: Agios, AstraZeneca, Bayer, BMS ; Research grant / Funding (self), Funding to self: IDMC: Genentech/Roche ; Research grant / Funding (institution): Agios, AstraZeneca, Bayer, BMS, Eli Lilly, Exelixis, EMD Serono, Medimmune, Merck, Novartis, QED, Taiho. M. Mangeshkar: Full / Part-time employment: Exelixis; Shareholder / Stockholder / Stock options: Exelixis. A-L. Cheng: Advisory / Consultancy, Advisory: Bayer Schering Pharma, Bristol-Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix Ltd., Roche/Genentech, and IQVIA; Advisory / Consultancy, Consultancy: Bayer Schering Pharma, Bristol-Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix Ltd., Roche/Genentech, and IQVIA; Honoraria (self): Bayer, Eisai, and Merck Sharp Dohme, Merck Serono, Novartis, Ono Pharmaceutical, Roche/Genentech, and IQVIA. A.B. El-Khoueiry: Advisory / Consultancy: Bayer, BMS, Agenus, Merck, EISAI, Pieris, EMD Serono, Exelixis, Roche/Genentech, Apeiron; Research grant / Funding (self): AstraZeneca, Astex. G.K. Abou-Alfa: Research grant / Funding (institution): ActaBiologica, Agios, Array, AstraZeneca, Bayer, Beigene, BMS, Casi, Celgene, Exelixis, Genentech, Halozyme, Incyte, Lilly, Mabvax, Novartis, OncoQuest, Polaris Puma, QED, 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.
Resources from the same session
238P - Laparoscopic cytoreduction in low disease burden, advanced-stage ovarian cancers: Experience from a tertiary cancer center
Presenter: Vikas Gupta
Session: Poster display session
Resources:
Abstract
239P - Impact of counseling on patient reported sexual adjustment following chemoradiation and brachytherapy for cervical cancer
Presenter: Vibhay Pareek
Session: Poster display session
Resources:
Abstract
240P - Morbidity and mortality of cervical cancer in the Republic of Kazakhstan
Presenter: Almagul Zhabagina
Session: Poster display session
Resources:
Abstract
241P - Impact of genomic alterations and HPV genotypes on clinical outcomes of Japanese patients with locally advanced cervical cancer
Presenter: Ikumi Kuno
Session: Poster display session
Resources:
Abstract
242P - Impact of combined interstitial and intracavitary brachytherapy in locally advanced cervical cancer: A survival and toxicity profile assessment
Presenter: Vibhay Pareek
Session: Poster display session
Resources:
Abstract
243P - Cervical cancer screening in sub-urban area of Banten and factor associated with uptake of screening
Presenter: Prio Wibisono
Session: Poster display session
Resources:
Abstract
245P - Factors influencing adherence to cryotherapy following positive VIA result as cervical cancer prevention in Temanggung, Central Java, Indonesia
Presenter: Herindita Puspitaningtyas
Session: Poster display session
Resources:
Abstract
246P - The main of reasons of advanced stage cervical cancer in Uzbekistan
Presenter: Zakhirova Nargiza
Session: Poster display session
Resources:
Abstract
247P - Role of ADC values in assessing response after chemoradiotherapy in cervix cancer and in identifying residual disease
Presenter: Venkata Pradeep Babu Koyyala
Session: Poster display session
Resources:
Abstract
248P - Retrospective review of metastatic carcinoma of cervix from a tertiary cancer institute of south India
Presenter: Arkoprovo Halder
Session: Poster display session
Resources:
Abstract