CELESTIAL: A randomized, double-blind, phase 3 trial of 2L+ patients with HCC1,2
The pivotal trial of >700 patients was initiated in 2013 to address the unmet needs in HCC2,3*
*At the start of the CELESTIAL trial (2013), there was no standard-of-care treatment post sorafenib.4
†707 patients were randomized at the time of the second interim analysis for OS. In total, CELESTIAL enrolled 773 patients.2
- Pathologic diagnosis of HCC not amenable to curative treatment
- Child-Pugh A
- Received prior sorafenib
- Prior treatment with 1-2 systemic therapies, with progression following at least 1
- ECOG PS of 0 or 1
- Disease etiology (HBV with or without HCV, HCV without HBV, other)
- Region (Asia, other)
- Presence of macrovascular invasion and/or extrahepatic spread of disease (yes, no)
CELESTIAL had a broad population and did not exclude patients based on5:
- Bile duct invasion
- Main portal vein invasion
- >50% liver involvement
- Prior immunotherapy
- Intolerance to prior systemic therapy
- AFP level
- Viral load
AFP=alpha-fetoprotein tumor marker; ECOG=Eastern Cooperative Oncology Group; HBV=hepatitis B virus; HCC=hepatocellular carcinoma; HCV=hepatitis C virus; PS=performance status.
CELESTIAL included a broad range of HCC patients2,5
BASELINE PATIENT CHARACTERISTICS
|Median age, years (range)||64 (22-86)||64 (24-86)|
|Male/Female||379 (81) / 91 (19)||202 (85) / 35 (15)|
|Asia / Europe||116 (25) / 231 (49)||59 (25) / 108 (46)|
|United States and Canada||108 (23)||59 (25)|
|Australia and New Zealand||15 (3)||11 (5)|
|White/Asian||264 (56) / 159 (34)||130 (55) / 82 (35)|
|Black or African American||8 (2)||11 (5)|
|Other and Not Reported||39 (9)||14 (6)|
|Number of prior systemic anticancer regimens for HCC|
|1||335 (71)||174 (73)|
|2||130 (28)||62 (26)|
|≥3||2 (<1)||1 (<1)|
|Etiology of disease|
|HBV||178 (38)||89 (38)|
|HCV||113 (24)||55 (23)|
|Dual HBV/HCV infection||8 (2)||4 (2)|
|Alcohol||112 (24)||39 (16)|
|Nonalcoholic steatohepatitis||43 (9)||23 (10)|
|Other and Unknown||99 (21)||63 (27)|
|ECOG performance status|
|0/1/2||245 (52) / 224 (48) / 1 (<1)||131 (55) / 106 (45) / 0|
|B (intermediate) / C (advanced)||42 (9) / 427 (91)||23 (10) / 214 (90)|
|<400 ng/mL||278 (59)||136 (57)|
|≥400 ng/mL||192 (41)||101 (43)|
|Extrahepatic spread of disease||369 (79)||182 (77)|
|Macrovascular invasion||129 (27)||81 (34)|
|Extrahepatic spread of disease and/or macrovascular invasion||398 (85)||200 (84)|
|Local liver-directed non-radiation anticancer therapy||209 (44)||113 (48)|
|Total duration of treatment of prior sorafenib, median, months||5.3||4.8|
BCLC=Barcelona Clinic Liver Cancer.
Among patients who received CABOMETYX, 71% were 2L5
First and only TKI with proven, significant OS and PFS in a broad, 2L+ HCC population1
CI=confidence interval; HR=hazard ratio; ITT=intent to treat; TKI=tyrosine kinase inhibitor.
In a prespecified exploratory subgroup analysis of patients who received only 1 prior systemic therapy
CABOMETYX exceeded 11 months median OS and 5 months median PFS in the second line2,5
‡No statistical procedure was employed for controlling type I error. Results should be considered hypothesis generating.2
CABOMETYX improved tumor control for patients with HCC6
With CABOMETYX, 47% of patients experienced tumor shrinkage in the ITT analysis§
REDUCTION IN TARGET LESION FROM BASELINE
- Each vertical line corresponds to 1 patient. The plot represents the best percentage change in tumor size from baseline in the evaluable patient population as determined by the Investigators, per RECIST v1.1
- Among patients with baseline and postbaseline target-lesion assessment, 222 out of 388 patients on the CABOMETYX arm and 27 out of 205 patients on the placebo arm had a decrease from baseline
§Stars denote confirmed partial responses.
Subjects are not represented due to: lack of evaluable postbaseline assessment, censoring (per PFS rules) before first evaluable postbaseline assessment, lack of target lesions, and/or incomplete or inevaluable target-lesion assessment. Data from time points after the first date of any of the censoring events defined for the primary PFS analysis were excluded.3
With CABOMETYX, 64% of patients achieved disease control2
SECONDARY ENDPOINT: ORR (ITT)1,5
|Best overall response||CABOMETYX
|Stable disease||282 (60)||78 (33)|
|Progressive disease||98 (21)||131 (55)|
|Not evaluable or missing||72 (15)||27 (11)|
- All responses were confirmed partial responses, as assessed by the Investigators per RECIST v1.11
- Disease control rate was defined as the percentage of patients with a complete response, partial response, or stable disease, as measured by RECIST v1.11,2
ORR=objective response rate; RECIST=Response Evaluation Criteria In Solid Tumors.
No new safety signals were observed with CABOMETYX in the CELESTIAL trial1
- The safety profiles across 3 pivotal trials in aRCC and HCC have been generally consistent with that of the initial CABOMETYX product approval
ARs occurring at a higher incidence in patients treated with CABOMETYX (Between-arm difference of ≥5% [All Grades] or ≥2% [Grade 3-4])1
|Percentage (%) of Patients|
|All Grades¶||Grade 3-4||All Grades¶||Grade 3-4|
|Metabolism and Nutrition|
|Skin and Subcutaneous Tissue|
|Respiratory, Thoracic, and Mediastinal|
|Musculoskeletal and Connective Tissue|
|Pain in extremity||9||<1||4||1|
¶National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.
#Includes the following terms: rash, rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, rash vesicular, dermatitis, dermatitis acneiform, dermatitis contact, dermatitis diaper, dermatitis exfoliative, dermatitis infected.
**Includes the following terms: hypertension, blood pressure diastolic increased, blood pressure increased.
Laboratory abnormalities occurring at a higher incidence in patients treated with CABOMETYX (Between-arm difference of ≥5% [All Grades] or ≥2% [Grade 3-4])1
|Percentage (%) of Patients|
|All Grades||Grade 3-4||All Grades||Grade 3-4|
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AR=adverse reaction; aRCC=advanced renal cell carcinoma; AST=aspartate aminotransferase; LDH=blood lactate dehydrogenase; PPE=palmar-plantar erythrodysesthesia.
National Comprehensive Cancer Network® (NCCN®)
Category 1: Based upon high-level evidence, there is uniform consensus that the intervention is appropriate.
llData reflect use after sorafenib.
The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.