Abstract 5907
Background
Extrahepatic spread (EHS) and macrovascular invasion (MVI) are poor prognostic factors in HCC. In the CELESTIAL trial (NCT01908426), C improved overall survival (OS) and progression-free survival (PFS) vs P in patients (pts) with previously treated advanced HCC. Median OS was 10.2 mo with C vs 8.0 mo with P (HR, 0.76; 95% CI, 0.63–0.92; P = 0.0049). Median PFS was 5.2 mo with C versus 1.9 mo with P (HR, 0.44; 95% CI, 0.36–0.52; P < 0.0001). Here, we analyze OS and PFS based on (i) EHS, (ii) MVI, and (iii) the sum of target lesion diameters (SOD) at baseline.
Methods
A total of 707 pts, stratified by disease etiology, geographic region, and the presence of EHS and/or MVI, were randomized 2:1 to receive C, 60 mg once daily (N = 470) or P (N = 237). Eligible patients had a pathologic diagnosis of HCC, Child-Pugh score A, and ECOG performance status ≤1. Pts received prior sorafenib and ≤2 lines of prior systemic therapy. Tumors were assessed every 8 weeks by investigator.
Results
In the overall population, 78% pts had EHS, 30% had MVI and 85% had EHS and/or MVI. Among pts with EHS, 50% had metastasis to the lung, 40% to lymph nodes and 17% to bones. C improved OS (HR ≤ 0.8) vs P in pts with or without MVI (Table). C also improved OS vs P in pts with EHS or high SOD. PFS was improved with C irrespective of the extent of the disease.Table: 703P
| No. pts | Median OS, mo | OS HR (95% CI) | Median PFS, mo | PFS HR (95% CI) | ||||
|---|---|---|---|---|---|---|---|---|
| C | P | C | P | C | P | |||
| EHS | ||||||||
| Yes | 369 | 182 | 9.6 | 6.9 | 0.72 (0.58-0.89) | 5.0 | 1.9 | 0.46 (0.37-0.56) |
| No | 101 | 55 | 12.0 | 12.3 | 0.96 (0.63-1.46) | 5.4 | 1.9 | 0.45 (0.31-0.66) |
| MVI | ||||||||
| Yes | 129 | 81 | 7.6 | 5.3 | 0.75 (0.54-1.03) | 3.7 | 1.8 | 0.42 (0.31-0.58) |
| No | 339 | 156 | 12.4 | 9.7 | 0.80 (0.64-1.01) | 5.5 | 1.9 | 0.48 (0.38-0.59) |
| SOD | ||||||||
| < median | 231 | 120 | 12.5 | 10.5 | 0.94 (0.71-1.24) | 5.5 | 1.9 | 0.48 (0.37-0.61) |
| ≥ median | 234 | 117 | 8.2 | 5.3 | 0.58 (0.45-0.76) | 4.2 | 1.9 | 0.44 (0.34-0.57) |
Conclusions
C generally improved OS in pt subgroups defined by extent of disease burden. The presence of MVI, EHS, or high SOD at baseline was associated with shorter OS in both treatment groups.
Clinical trial identification
NCT01908426.
Legal entity responsible for the study
Exelixis.
Funding
Exelixis, Inc.
Editorial Acknowledgement
Disclosure
J.F. Blanc: Consulting or advisory role: Bayer, SP, BMS, Ipsen. T. Meyer: Consulting or advisory role: Bayer, BTG, Ipsen; Research funding: Bayer, BTG. A-L. Cheng: Consulting or Advisory role: Bayer Schering Pharma, Bristol-Myers Squibb, Eisai, Merck. Serono, Novartis, Ono Pharmaceutical, Onxeo; Speakers\' bureau: Novartis; Research funding: Sanofi. A.B. El-Khoueiry: Honoraria: BMS, Bayer, Exelixis, EMD Serono, EISAI, Roche, Cytomx, Merck. Consulting or advisory role: BMS, Bayer; Research funding: AstraZeneca, Astex. L. Bolondi: Consulting or advisory role: Bayer, BMS, Sirtex, Guerbet; Speakers bureau: Bayer, BMS, Sirtex, Bracco, Eli-Lilly, Guerbet, Meda-Pharm; Travel accommodations expenses: Bayer, BMS, Bracco, Sirtex, Guerbet, Eli-Lilly. V. Dadduzio: Travel, accommodations, expenses: Bayer, Amgen, Astellas. A. Baron: Speakers\' bureau: BMS, Merck, Genentech, Lilly. J. Adriani: Employee, Stock ownership: Exelixis. R.K. Kelly: Consulting or advisory role: Genentech for IDMC (self); Bayer, BMS, AstraZeneca, DebioPharm, Agios; Research funding: Adaptimmune, Agios, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Exelixis, Eli Lilly, Medimmune, Merck, Novartis, Regeneron, Sanofi, Taiho, Target Pharma Solutions, Tekmira. G.K. Abou-Alfa: Self consulting role: Agios, Amgen, Antengene, Aptus, Aslan, Astellas, AstraZeneca, Bayer, BMS, Boston Scientifc, Carsgen, Celgene, Casi, Daiichi, Debio, Delcath, Eisai, Exelixis, Halozyme, Inovio, Ipsen, Merck, Onxeo, PCI Biotech, Roche, Sanofi, Servier, Sillajen, Sirtex, Yakult Immediate; Family member consulting: Celgene, CytomX, Gilead, Halozyme, Sanofi, Silenseed; Institutional Research; Agios, Array, AstraZeneca, Bayer, BMS, Casi, Celgene, Exelixis, Genentech, Incyte, Lilly, Mabvax, Medimmune, Momenta, Novartis, OncoMed Pharmaceuticals, Roche. All other authors have declared no conflicts of interest.