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– Accepted as a late-breaking oral presentation at the 2018
American Society of Clinical Oncology’s Gastrointestinal Cancers
– Cabozantinib previously granted orphan drug designation for the
treatment of hepatocellular carcinoma (HCC) by
Abstract 207: Cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) who have received prior sorafenib: results from the randomized phase 3 CELESTIAL trial.
Ghassan K. Abou-Alfa, MD,
About the CELESTIAL Study
CELESTIAL is a randomized, double-blind, placebo-controlled study of
cabozantinib in patients with advanced HCC conducted at more than 100
sites globally in 19 countries. The trial was designed to enroll 760
patients with advanced HCC who received prior sorafenib and may have
received up to two prior systemic cancer therapies for HCC and had
adequate liver function. Enrollment of the trial was completed in
The primary endpoint for the trial is OS, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.
Based on available clinical trial data from various published trials conducted in the second-line setting of advanced HCC, the CELESTIAL trial statistics for the primary endpoint of OS assumed a median OS of 8.2 months for the placebo arm. A total of 621 events provide the study with 90 percent power to detect a 32 percent increase in median OS (HR = 0.76) at the final analysis. Two interim analyses were planned and conducted at 50 percent and 75 percent of the planned 621 events.
Liver cancer is the third-leading cause of death worldwide, and hepatocellular carcinoma (HCC) is the most common form, making up about three-fourths of the nearly 41,000 cases that will be diagnosed in 2017 in the U.S.1,2 Without treatment, patients with advanced disease usually survive less than 6 months, and it is estimated that 29,000 people will die due to liver cancer in the U.S.3 Worldwide, nearly 800,000 new cases are diagnosed annually, and the disease accounts for more than 700,000 deaths each year.4
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in
CABOMETYX is not indicated for the treatment of advanced HCC.
Please see Important Safety Information below and full U.S. prescribing information at https://cabometyx.com/downloads/cabometyxuspi.pdf.
U.S. Important Safety Information
- Severe Hemorrhage occurred with CABOMETYX. In two RCC studies, Grade ≥3 hemorrhagic events occurred in 2.1% of CABOMETYX patients vs 1.6% with everolimus and in 5.1% of CABOMETYX patients vs 1.4% with sunitinib. Fatal hemorrhages also occurred in the cabozantinib clinical program. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
- Gastrointestinal (GI) Perforations and Fistulas were reported with CABOMETYX. In two RCC studies, GI perforations occurred in 0.9% of CABOMETYX patients vs 0.6% with everolimus and in 2.6% of CABOMETYX patients vs 0% with sunitinib. Fatal perforations occurred in the cabozantinib clinical program. Fistulas were reported in 1.2% (including 0.6% anal fistula) of CABOMETYX patients vs 0% with everolimus. Monitor patients for symptoms of perforations and fistulas. Discontinue CABOMETYX in patients who experience a GI perforation or a fistula that cannot be appropriately managed.
- Thrombotic Events increased with CABOMETYX. In two RCC studies, arterial thromboembolism events were reported in 0.9% of CABOMETYX patients vs 0.3% with everolimus and 1.3% of CABOMETYX patients vs 5.6% with sunitinib. Pulmonary embolism events were reported in 3.9% of CABOMETYX patients vs 0.3% with everolimus and 9% of CABOMETYX patients vs 0% with sunitinib. Venous thromboembolism occurred in 7.3% of CABOMETYX patients vs 2.5% with everolimus. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction, cerebral infarction, or other serious arterial thromboembolic complication.
- Hypertension and Hypertensive Crisis occurred with CABOMETYX. In two RCC studies, treatment-emergent hypertension increased with CABOMETYX. Hypertension was reported in 37% (15% Grade ≥3) of CABOMETYX patients vs 7.1% (3.1% Grade ≥3) with everolimus and in 67% (28% Grade ≥3) of CABOMETYX patients vs 44% (21% Grade ≥3) with sunitinib. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for hypertensive crisis or severe hypertension that cannot be controlled with antihypertensive therapy or medical management.
- Diarrhea occurred with CABOMETYX. In two RCC trials, diarrhea occurred in 74% (11% Grade 3) of CABOMETYX patients vs 28% (2% Grade 3) with everolimus and in 73% (10% Grade 3) of CABOMETYX patients vs 54% (11% Grade 3) with sunitinib. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose.
- Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurred with CABOMETYX. In two RCC trials, PPES occurred in 42% (8.2% Grade 3) of CABOMETYX patients vs 6% (<1% Grade 3) with everolimus and in 42% (7.7% Grade 3) of CABOMETYX patients vs 33% (4.2% Grade 3) with sunitinib. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume CABOMETYX at a reduced dose.
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
- Embryo-fetal Toxicity may be associated with CABOMETYX. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.
- Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPES, weight decreased, vomiting, dysgeusia, and stomatitis.
- Drug Interactions: Strong CYP3A4 inhibitors and inducers: Reduce the dosage of CABOMETYX if concomitant use with strong CYP3A4 inhibitors cannot be avoided. Increase the dosage of CABOMETYX if concomitant use with strong CYP3A4 inducers cannot be avoided.
- Lactation: Advise women not to breastfeed while taking CABOMETYX and for 4 months after the final dose.
- Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.
Founded in 1994,
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: Exelixis’ plan to submit an
supplemental New Drug Application to the
Hepatocellular Carcinoma –
United States, 2001-2006. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5917a3.htm. Accessed November 2017.
American Cancer Society: Cancer Facts and Figures 2017. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2017/cancer-facts-and-figures-2017.pdf. Accessed November 2017.
- Weledji E, Orock G, Ngowe M, NsaghaD. How grim is hepatocellular carcinoma? Annals of Medicine and Surgery. 2014. (3):71-76.
Estimated cancer incidence, mortality and prevalence worldwide.
International Agency for Research on Cancer, GLOBOCAN 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed November 2017.
Susan Hubbard, 650-837-8194
EVP, Public Affairs and Investor Relations
Claire McConnaughey, 650-837-7052
Senior Manager, Public Affairs