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– Thyroid cancer is the most rapidly increasing cancer in the U.S., with incidence tripling over the past 30 years –
“Cabozantinib has demonstrated encouraging clinical activity in patients
with radioiodine-refractory differentiated thyroid cancer in phase 1 and
2 studies, suggesting it may be a promising treatment option for
patients who have progressed after prior VEGFR-targeting therapy,” said
COSMIC-311 is a multicenter, randomized, double-blind, placebo-controlled phase 3 pivotal trial that aims to enroll approximately 300 patients at approximately 150 sites globally. Patients will be randomized in a 2:1 ratio to receive either cabozantinib 60 mg or placebo once daily.
“With the incidence of thyroid cancer increasing more rapidly than any
other type of cancer in the U.S., and limited options available to
patients whose disease has progressed following anti-VEGFR therapy,
there is an urgent need for new treatments,”said
More information about this trial is available at ClinicalTrials.gov.
About Differentiated Thyroid Carcinoma
Thyroid cancer is commonly diagnosed at a younger age than most other adult cancers and is the most rapidly increasing cancer in the U.S., tripling in incidence in the past three decades.1 Approximately 54,000 new cases of thyroid cancer will be diagnosed in the U.S. in 2018.1 Nearly three out of four of these cases will be in women.1 Cancerous thyroid tumors include differentiated, medullary and anaplastic forms.1
Differentiated thyroid tumors, which make up about 90 percent of all thyroid cancers, are typically treated with surgery followed by ablation of the remaining thyroid with radioiodine.2 Approximately 5 to 15 percent of differentiated thyroid tumors are resistant to radioiodine treatment.3 For these patients, life expectancy is only three to six years from the time metastatic lesions are detected.4,5,6
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in
CABOMETYX is not indicated for radioiodine-refractory DTC.
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.
Founded in 1994,
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: the potential of cabozantinib
as a treatment option for patients with radioiodine-refractory
differentiated thyroid cancer who have progressed after prior
VEGFR-targeting therapy; and Exelixis’ plans to reinvest in its business
to maximize the potential of the company’s pipeline, including through
targeted business development activities and internal drug discovery.
Any statements that refer to expectations, projections or other
characterizations of future events or circumstances are forward-looking
statements and are based upon Exelixis’ current plans, assumptions,
beliefs, expectations, estimates and projections. Forward-looking
statements involve risks and uncertainties. Actual results and the
timing of events could differ materially from those anticipated in the
forward-looking statements as a result of these risks and uncertainties,
which include, without limitation: risks and uncertainties related to
regulatory review and approval processes and Exelixis’ compliance with
applicable legal and regulatory requirements; the potential failure of
cabozantinib to demonstrate safety and/or efficacy in COSMIC-311;
uncertainties inherent in the product development process, including
evolving regulatory requirements, slower than anticipated patient
enrollment or inability to identify a sufficient number of clinical
trial sites; the costs of conducting clinical trials, including
Exelixis’ dependence on third-party vendors for the development,
manufacture and supply of cabozantinib; Exelixis’ ability to protect its
intellectual property rights; market competition; changes in economic
and business conditions; and other factors affecting
2 Cooper DS, et al. 2009.
3 Worden F. 2014. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Ther Adv Med Oncol. 6:267–279.
4 Xing M, Haugen BR, Schlumberger M. 2013.
5 Pacini F, et al. 2012. Radioactive iodine-refractory differentiated thyroid cancer: unmet needs and future directions. Expert Rev Endocrinol Metab. 7:541–554.
6 Durante C, et al. 2006. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 91:2892–2899.
Susan Hubbard, 650-837-8194
EVP, Public Affairs and
Lindsay Treadway, 650-837-7522
Senior Director, Public Affairs and Advocacy Relations