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– 54 percent objective response rate and 43 percent stable disease observed among 35 evaluable patients –
– Results to be presented during an oral session on
Patients with metastatic, RAI-refractory DTC were enrolled in this single-arm, open-label trial, and were administered oral cabozantinib 60 mg once daily. The primary endpoint of the trial is objective response rate. Among the 35 patients who were evaluable for response, partial response was achieved by 54 percent of patients (n=19), and stable disease was reported in 43 percent of patients (n=15) per RECIST 1.1. All but one evaluated patient experienced a decrease in tumor target lesions. Secondary endpoints of the trial include progression-free survival (PFS), time to progression (TTP), duration of response (DOR) and clinical benefit rate (CBR) defined as the number of patients achieving an objective response or stable disease for at least 6 months. The CBR at six months was 80 percent (n=28). With a median follow up for the study of 35 weeks the median PFS has not been reached. The median TTP among those patients who progressed was 35 weeks.
“While many patients with differentiated thyroid cancer can be treated
successfully with radioiodine, there are very few options for those
patients whose tumors have become resistant to treatment,” said
“We are dedicated to supporting investigator-sponsored trials focused on
evaluating cabozantinib in a range of tumor types to help inform our
ongoing development program whose main goal is to provide improved
treatment options to patients in need,” said
The most common treatment-related adverse events included hyperglycemia (80 percent), diarrhea (77 percent), malaise/fatigue (74 percent), and weight loss (71 percent). The majority of these adverse events were grade 1 or 2. The most comment grade 3-5 adverse events occurring in more than one patient included hypertension (14 percent), increased lipase (9 percent), pulmonary embolism (6 percent), and hyponatremia (6 percent).
About the Trial
The IST is being conducted by the
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.4-6
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in
CABOMETYX is not indicated for the treatment of differentiated thyroid carcinoma.
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,
Exelixis Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: Exelixis’ plans to initiate a
pivotal phase 3 trial with cabozantinib in patients with advanced DTC
later this year; the future presentation of data results from a phase 2
IST of cabozantinib for the first-line treatment of metastatic
radioiodine (RAI)-refractory DTC at the 2018 Multidisciplinary Head and
Neck Cancers Symposium; the clinical and therapeutic potential of
cabozantinib for patients with DTC; Exelixis’ continued support of ISTs
focused on evaluating cabozantinib in a range of tumor types; Exelixis’
goal to provide improved treatment options to patients in need; and
Exelixis’ commitment to reinvesting in its business to maximize the
potential of its pipeline, including supplementing its existing
therapeutic assets through targeted business development activities and
internal drug discovery. Words such as “plan,” “will,” “may,” “focused,”
“goal,” “potential,” “future,” “commitment,” “intend,” or other similar
expressions identify forward-looking statements, but the absence of
these words does not necessarily mean that a statement is not
forward-looking. In addition, any statements that refer to expectations,
projections or other characterizations of future events or circumstances
are forward-looking statements. These forward-looking statements 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: the potential failure of cabozantinib to demonstrate safety
and efficacy in clinical testing; the availability of data at the
referenced times; Exelixis’ ability and the ability of its collaborators
to conduct clinical trials of cabozantinib sufficient to achieve a
positive completion; the complexities and challenges associated with
regulatory review and approval processes; the level of costs associated
with Exelixis’ commercialization, research and development and other
activities; competition in the area of business development activities
and the inherent uncertainty of the drug discovery process; Exelixis’
dependence on its relationships with its cabozantinib collaboration
partners, including, the level of their investment in the resources
necessary to successfully commercialize cabozantinib in the territories
where it is approved; Exelixis’ dependence on its relationship with
Genentech/Roche with respect to cobimetinib and Exelixis’ ability to
maintain its rights under the collaboration; market acceptance of
CABOMETYX, COMETRIQ, and COTELLIC and the availability of coverage and
reimbursement for these products; Exelixis’ dependence on third-party
vendors for the development, manufacture and supply of its products;
Exelixis’ ability to protect the company’s intellectual property rights;
market competition; changes in economic and business conditions, and
other factors discussed under the caption “Risk Factors” in Exelixis’
quarterly report on Form 10-Q filed with the Securities and Exchange
American Cancer Society. Key Statistics for Thyroid Cancer. https://www.cancer.org/cancer/thyroid-cancer/about/key-statistics.html. Accessed January 2018.
Cooper DS, et al. 2009.
Revised American Thyroid Associationmanagement guidelines for patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association(ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 19:1167–1214.
- Worden F. 2014. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Ther Adv Med Oncol 6:267–279.
Xing M, Haugen BR, Schlumberger M. 2013.
Progressin molecular-based management of differentiated thyroid cancer. Lancet 381:1058–1069.
- Pacini F, et al. 2012. Radioactive iodine-refractory differentiated thyroid cancer: unmet needs and future directions. Expert Rev Endocrinol Metab 7:541–554.
- 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 Investor Relations
Lindsay Treadway, 650-837-7522
Director, Public Affairs and Advocacy Relations