Press Release
Press Release
Exelixis Announces Results from Sub-Group Analyses of the Phase 3 Pivotal CELESTIAL Trial of Cabozantinib for Advanced Hepatocellular Carcinoma Presented at ASCO 2018
– Cabozantinib improved overall survival and progression-free survival irrespective of duration of prior sorafenib treatment or age category –
“We’re pleased with the encouraging CELESTIAL subgroup data presented at
Outcomes in Patients who had Received Sorafenib [abstract 4088]
The sub-analysis of patients in CELESTIAL who received sorafenib as
their only prior systemic therapy was presented by
Duration of Prior Sorafenib* | |||||||||||||||||||
<3 Months | 3 to <6 Months | ≥6 Months | |||||||||||||||||
Cabozantinib |
Placebo |
Cabozantinib |
Placebo |
Cabozantinib |
Placebo |
||||||||||||||
Median OS (months) | 8.9 | 6.9 | 11.5 | 6.5 | 12.3 | 9.2 | |||||||||||||
HR 0.72, 95 percent CI 0.47–1.10 |
HR 0.65, 95 percent CI 0.43–1.00 |
HR 0.82, 95 percent CI 0.58–1.16 |
|||||||||||||||||
Median PFS (months) | 3.8 | 1.8 | 5.4 | 1.9 | 5.7 | 1.9 | |||||||||||||
HR 0.35, 95 percent CI 0.23–0.52 |
HR 0.37, 95 percent CI 0.25–0.56 |
HR 0.48, 95 percent CI 0.35–0.67 |
|||||||||||||||||
*Patients who received prior sorafenib as the only prior systemic therapy for HCC HR=Hazard Ratio; CI=Confidence Interval |
|||||||||||||||||||
Treatment-related grade 3 or 4 adverse events (AEs) that occurred in at least 5 percent of any patient group were palmar-plantar erythrodysesthesia, aspartate aminotransferase increased, hypertension, fatigue, decreased appetite, diarrhea, asthenia and anemia.
Outcomes in Patients Based on Age [abstract 4090]
The sub-analysis evaluating patients in the CELESTIAL trial based on age
was presented by
Patients <Age 65 | Patients ≥65 | ||||||||||||
Cabozantinib (n=240) |
Placebo
(n=124) |
Cabozantinib
(n=230) |
Placebo
(n=113) |
||||||||||
Median OS (months) | 9.6 | 7.7 | 11.1 | 8.3 | |||||||||
HR 0.81, 95 percent CI 0.62–1.05 | HR 0.74, 95 percent CI 0.56–0.97 | ||||||||||||
Median PFS (months) | 5.0 | 1.9 | 5.4 | 2.0 | |||||||||
HR 0.45, 95 percent CI 0.35–0.57 | HR 0.46, 95 percent CI 0.35–0.59 | ||||||||||||
Treatment-related grade 3 or 4 AEs occurred in at least 5 percent of either age group and were similar in nature and frequency to the AEs that occurred in patients who received sorafenib as their only prior systemic therapy.
An encore of the CELESTIAL trial data originally presented at the 2018
The CELESTIAL trial was the basis for Exelixis’ supplemental New Drug
Application filed with the
About the CELESTIAL Study
CELESTIAL is a phase 3 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
Results of the trial were first presented by Dr.
About HCC
Liver cancer is the second-leading cause of cancer death worldwide, accounting for more than 700,000 deaths and nearly 800,000 new cases each year.1 In the U.S., the incidence of liver cancer has more than tripled since 1980.2 HCC is the most common form of liver cancer, making up about three-fourths of the estimated nearly 42,000 new cases in the U.S. in 2018. HCC is the fastest-rising cause of cancer-related death in U.S.3 Without treatment, patients with advanced HCC usually survive less than 6 months.4
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in
Please see Important Safety Information below and full U.S. prescribing information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
U.S. Important Safety Information
- Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic events was 3% in CABOMETYX-treated patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
- Gastrointestinal (GI) Perforations and Fistulas: In RCC studies, fistulas were reported in 1% of CABOMETYX-treated patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, gastrointestinal (GI) perforations were reported in 1% of CABOMETYX-treated patients. Monitor patients for symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula which cannot be appropriately managed or a GI perforation.
- Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. In RCC studies, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
- Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension, including hypertensive crisis. In RCC studies, hypertension was reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. 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 severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
- Diarrhea: In RCC studies, diarrhea occurred in 74% of patients treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients treated with CABOMETYX. 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 (PPE): In RCC studies, palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE 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. Perform an evaluation for RPLS in any patient 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, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.
- Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
- Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
- 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.
Please see accompanying full Prescribing Information https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
About
Founded in 1994,
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: the regulatory review
process, including Exelixis’ intent to continue to work closely with the
_______________________________
1 Cancer
Incidence and Mortality Worldwide. Liver Cancer.
2
3 Mittal S, El-Serag HB.
Epidemiology of HCC: Consider the Population.
4 Weledji E, Orock
G, Ngowe M, NsaghaD. How grim is hepatocellular carcinoma? Annals of
Medicine and Surgery. 2014. 3:71-76.
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Source:
Exelixis, Inc.
Investors:
Susan Hubbard,
650-837-8194
EVP, Public Affairs and Investor Relations
shubbard@exelixis.com
or
Media:
Lindsay
Treadway, 650-837-7522
Senior Director, Public Affairs and
Advocacy Relations
ltreadway@exelixis.com