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The safety and efficacy of CABOMETYX® (cabozantinib) were evaluated in patients with advanced hepatocellular carcinoma (HCC) not amenable to curative treatment and who had previously received sorafenib in the randomised, double-blind, placebo-controlled phase III CELESTIAL study.1,10
View the CELESTIAL trial publicationThe CELESTIAL trial was a phase III, double blind, randomised controlled trial, conducted in a previously-treated advanced hepatocellular carcinoma (HCC) population.10
In total, 1023 patients were assessed for eligibility and 707 patients were randomly assigned in 2:1 ratio to receive cabozantinib 60 mg/day (n=470) or a matched placebo (n=237). Patients were stratified according to pre-specified categories: disease aetiology, region and the presence of macrovascular invasion (MVI) and/or extrahepatic spread (EHS).10
Within the cabozantinib treatment group, 71% of patients received cabozantinib as second-line treatment and 28% as a third-line treatment. These patients had previously undergone one systemic anticancer regimen for advanced HCC.10
The primary endpoint was OS. The secondary endpoints were progression-free survival (PFS), the objective response rate (ORR), and safety. Tumour assessment took place every 8 weeks using computed tomography or magnetic resonance imaging (MRI). Measurable disease was defined by the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Assessments took place until 8 weeks after radiographic progression or until CABOMETYX®or placebo had been discontinued, which ever occurred later.10
Design of the CELESTIAL phase III trial
HCC, hepatocellular carcinoma; ORR, objective response rate; OS, overall survival; PFS, progression-free survival
Adapted from Abou-Alfa GK, et al. 201810
Study design
The study population included 707 patients previously treated for advanced HCC.10
Patients were included if they met the following criteria:10
Patients were excluded if they met the following criteria:10
Baseline characteristics were balanced between the cabozantinib and placebo groups as shown in the table.10
Patient demographic and baseline characteristics in the CELESTIAL phase III trial
Characteristic |
Cabozantinib (n=470) |
Placebo (n=237) |
Gender, n (%) | ||
Male | 378 (81) | 202 (85) |
Female | 91 (19) | 35 (15) |
Age, years | ||
Median | 64 | 64 |
Range | 22-86 | 24-86 |
ECOG PS, n (%) | ||
0 | 245 (52) | 131 (55) |
1 | 224 (48) | 106 (45) |
2 | 1 (<1) | 0 (0) |
Etiologic factor, n (%) | ||
HBV | 178 (38) | 89 (38) |
HCV | 113 (24) | 55 (23) |
Dual HBV and HCV infection | 8 (2) | 4 (2) |
Alcohol use | 112 (24) | 39 (16) |
Nonalcoholic steatohepatitis | 43 (9) | 23 (10) |
Other | 24 (5) | 16 (7) |
Unknown | 75 (16) | 47 (20) |
EHS of disease, n (%) |
||
369 (79) | 182 (77) | |
MVI, n (%) | ||
129 (27) | 81 (34) | |
EHS of disease, MVI or both, n (%) | ||
398 (85) | 200 (84) |
ECOG PS, Eastern Cooperative Oncology Group performance score; EHS, extrahepatic spread; HBV, hepatitis B virus; HCV, hepatitis C virus, MVI, macrovascular invasion.
Adapted from Abou-Alfa GK, et al. 201810
Patient Population
Cabozantinib significantly extended OS in advanced HCC patients vs. placebo: 10.2 months (95% CI: 9.1–12.0) for cabozantinib vs. 8.0 months (95% CI: 6.8–9.4) for placebo.10
OS in the advanced HCC population in the CELESTIAL phase III trial
OS, overall survival
Adapted from Abou-Alfa GK, et al. 201810
In the subgroup analysis of patients previously treated with sorafenib only, cabozantinib provided an additional 4.1 months of OS vs. placebo (11.3 months for cabozantinib and 7.2 months for placebo). Risk of death was reduced by 30% in this population (stratified hazard ratio [HR] for death: 0.70; 95% CI: 0.55-0.88).10
OS in patients previously treated with sorafenib only in the CELESTIAL phase III trial
OS, overall survival
Adapted from Abou-Alfa GK, et al. 201810
Cabozantinib significantly improved PFS in advanced HCC patients: 5.2 months (95% CI: 4.0–5.5) vs. 1.9 months (95% CI: 1.9–1.9) for placebo.10
PFS in the advanced HCC population in the CELESTIAL phase III trial
PFS, progression-free survival
Adapted from Abou-Alfa GK, et al. 201810
In the subgroup analysis of patients previously treated with sorafenib only, cabozantinib provided an additional 3.6 months without signs of advanced HCC recurrence vs. placebo (5.5 months for cabozantinib and 1.9 months for placebo; HR for disease progression or death: 0.40; 95% CI: 0.32-0.50).10
PFS in patients previously treated with sorafenib only in the CELESTIAL phase III trial
PFS, progression-free survival
Adapted from Abou-Alfa GK, et al. 201810
The objective response rate according to RECIST, version 1.1, was 4% (18 partial responses among 470 patients) in the cabozantinib group and less than 1% (1 partial response among 237 patients) in the placebo group (P= 0.009). Cabozantinib enabled a high number of patients to achieve stable disease control versus placebo (64% vs. 33%, respectively).10
Disease Control in the Celestial phase III trial
Disease Control
Adapted from Abou-Alfa GK, et al. 201810
OS in subgroups of the CELESTIAL phase III trial
PFS in subgroups of the CELESTIAL phase III trial
AFP, alpha-fetoprotein; ECOG, Eastern Cooperative Oncology Group; EHS, extrahepatic spread of disease; HBV, hepatitis B virus; HCV, hepatitis C virus; MVI, macrovascular invasion
Adapted from Abou-Alfa GK, et al. 201810
Key efficacy results
Please see the ‘What are the adverse events of CABOMETYX®’ and ‘What are the dosing recommendations for CABOMETYX®’ sections of this website.
Please also refer to the CABOMETYX® Summary of Product Characteristics for a full list of adverse events and dose reduction recommendations.
For further information on the CELESTIAL trial, please refer to the full published clinical paper.10
Safety results
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