– CABOMETYX recommended for the treatment of previously untreated
advanced renal cell carcinoma across all patient risk groups –
ALAMEDA, Calif.--(BUSINESS WIRE)--Sep. 7, 2018--
Inc. (NASDAQ:EXEL) today announced that the National Comprehensive
Cancer Network (NCCN) updated its Clinical Practice Guidelines to
include new recommendations for CABOMETYX® (cabozantinib)
tablets. With the updates, CABOMETYX is recommended by the NCCN for the
treatment of advanced renal cell carcinoma (RCC) regardless of patient
risk status (favorable-, intermediate-, and poor-risk).
Key CABOMETYX-related highlights from the updated NCCN Clinical Practice
Guidelines for Kidney Cancer include:1
CABOMETYX is the only preferred tyrosine kinase inhibitor (TKI)
treatment option for first-line patients in the poor- and
intermediate-risk groups (Category 2A)
CABOMETYX is a recommended first-line treatment option for
favorable-risk patients (Category 2B)
CABOMETYX is the only preferred TKI treatment option for previously
treated patients (Category 1)
“CABOMETYX is the only TKI indicated for the treatment of advanced
kidney cancer with NCCN-preferred status for intermediate- and poor-risk
groups in the first-line setting and the only TKI with preferred status
for patients who have progressed on prior therapy,” said Michael M.
Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. “We
welcome these updated recommendations, which recognize the significance
of the CABOSUN trial data included in our label as an important advance
in the care of patients with this disease.”
The NCCN Clinical Practice Guidelines are the recognized standard for
clinical policy in cancer care and are developed through review of
evidence and recommendations from physicians and oncology researchers.
The NCCN kidney cancer panel’s decision to include CABOMETYX as a
Category 2A preferred option for the treatment of patients with
previously untreated advanced RCC with poor- or intermediate-risk
disease was based on the results of the phase 2 CABOSUN trial.
Additionally, in its recent update to the Clinical Practice Guidelines
for Hepatobiliary Cancers, the NCCN added cabozantinib as a Category 1
option for the treatment of patients with hepatocellular carcinoma (HCC)
(Child-Pugh Class A only) who have been previously treated with
sorafenib.2 CABOMETYX is not FDA-approved for previously
treated advanced HCC. On May 29, 2018, the U.S. FDA accepted the
supplemental New Drug Application for CABOMETYX in previously treated
advanced HCC and assigned it a Prescription Drug User Fee Act (PDUFA)
action date of January 14, 2019.
Please see Important Safety Information below and full U.S. prescribing
information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
About the CABOSUN Study
On May 23, 2016, Exelixis announced that the phase 2 CABOSUN study met
its primary endpoint, demonstrating a statistically significant and
clinically meaningful improvement in PFS compared with sunitinib in
patients with advanced intermediate- or poor-risk RCC as determined by
investigator assessment. The CABOSUN study was conducted by The Alliance
for Clinical Trials in Oncology and was sponsored by the National Cancer
Institute-Cancer Therapy Evaluation Program (NCI-CTEP) under
the Cooperative Research and Development Agreement with Exelixis for the
development of cabozantinib. These results were first presented by
Dr. Toni Choueiri at the European Society for Medical Oncology (ESMO)
2016 Congress, and published in the Journal of Clinical
Oncology (Choueiri, JCO, 2016).3 In June
2017, a blinded independent radiology review committee (IRC) confirmed
that cabozantinib provided a clinically meaningful and statistically
significant improvement in the primary efficacy endpoint of
investigator-assessed PFS. Results from the IRC review were presented by
Dr. Toni Choueiri at the ESMO 2017 Congress.
CABOSUN was a randomized, open-label, active-controlled phase 2 trial
that enrolled 157 patients with advanced RCC determined to be
intermediate- or poor-risk by the IMDC criteria. Patients were
randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib
(50 mg once daily, 4 weeks on followed by 2 weeks off). The primary
endpoint was PFS. Secondary endpoints included overall survival,
objective response rate and safety. Eligible patients were required to
have locally advanced or metastatic clear-cell RCC, ECOG performance
status 0-2 and had to be intermediate- or poor-risk per the IMDC
criteria (Heng, JCO, 2009).4 Prior systemic
treatment for RCC was not permitted.
About Advanced Renal Cell Carcinoma
The American Cancer Society’s 2018 statistics cite kidney cancer as
among the top ten most commonly diagnosed forms of cancer among both men
and women in the U.S.5 Clear cell RCC is the most common type
of kidney cancer in adults.6 If detected in its early stages,
the five-year survival rate for RCC is high; for patients with advanced
or late-stage metastatic RCC, however, the five-year survival rate is
only 12 percent, with no identified cure for the disease.7 Approximately
30,000 patients in the U.S. and 68,000 globally require treatment, and
an estimated 14,000 patients in the U.S. each year are in need of a
first-line treatment for advanced kidney cancer.7
The majority of clear cell RCC tumors have lower than normal levels of a
protein called von Hippel-Lindau, which leads to higher levels of MET,
AXL and VEGF.8,9 These proteins promote tumor angiogenesis
(blood vessel growth), growth, invasiveness and metastasis.10,11,12,13 MET
and AXL may provide escape pathways that drive resistance to VEGF
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.14 In the U.S., the incidence of liver cancer has
more than tripled since 1980.5 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 2018.5 HCC is the
fastest-rising cause of cancer-related death in U.S.15 Without
treatment, patients with advanced HCC usually survive less than 6 months.16
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in the United States for the treatment of
patients with advanced RCC. CABOMETYX tablets are also approved in the
European Union, Norway, Iceland, Australia, Switzerland and South Korea
for the treatment of advanced RCC in adults who have received prior
VEGF-targeted therapy, and in the European Union for previously
untreated intermediate- or poor-risk advanced RCC. In March 2017, the
FDA granted orphan drug designation to cabozantinib for the treatment of
advanced HCC. On March 28, 2018, Ipsen announced that the European
Medicines Agency validated its application for a new indication for
cabozantinib as a treatment for previously treated advanced HCC in the
European Union. In 2016, Exelixis granted Ipsen exclusive rights for the
commercialization and further clinical development of cabozantinib
outside of the United States and Japan. In 2017, Exelixis granted
exclusive rights to Takeda Pharmaceutical Company Limited for the
commercialization and further clinical development of cabozantinib for
all future indications in Japan.
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
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.
Founded in 1994, Exelixis, Inc. (Nasdaq: EXEL) is a commercially
successful, oncology-focused biotechnology company that strives to
accelerate the discovery, development and commercialization of new
medicines for difficult-to-treat cancers. Following early work in model
genetic systems, we established a broad drug discovery and development
platform that has served as the foundation for our continued efforts to
bring new cancer therapies to patients in need. We discovered our three
commercially available products, CABOMETYX® (cabozantinib), COMETRIQ®
(cabozantinib) and COTELLIC® (cobimetinib), and have entered into
partnerships with leading pharmaceutical companies to bring these
important medicines to patients worldwide. Supported by revenues from
our marketed products and collaborations, we are committed to prudently
reinvesting in our business to maximize the potential of our pipeline.
We are supplementing our existing therapeutic assets with targeted
business development activities and internal drug discovery - all to
deliver the next generation of Exelixis medicines and help patients
recover stronger and live longer. In July 2018, Exelixis was added to
the Standard & Poor’s (S&P) MidCap 400 index, which measures the
performance of profitable mid-sized companies. For more information
about Exelixis, please visit www.exelixis.com,
follow @ExelixisInc on
Twitter or like Exelixis,
Inc. on Facebook.
Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are
registered U.S. trademarks.
1 National Comprehensive Cancer Network Clinical Practice
Guidelines in Oncology. Kidney Cancer. Version 1.2019. Updated September
2 National Comprehensive Cancer Network
Clinical Practice Guidelines in Oncology. Hepatobiliary Cancers. Version
3.2018. Updated August 29, 2018.
3 Choueiri, T.K., et
al. Cabozantinib versus Sunitinib as Initial Targeted Therapy for
Patients with Metastatic Renal Cell Carcinoma of Poor or Intermediate
Risk: The Alliance A031203 CABOSUN Trial. Am J Clin Oncol.
4 Heng D.Y., Xie W., Regan M.M., et
al. Prognostic factors for overall survival in patients with metastatic
renal cell carcinoma treated with vascular endothelial growth
factor-targeted agents: Results from a large, multicenter study. Am
J Clin Oncol. 2009; 27:5794-5799.
5 American Cancer
Society: Cancer Facts and Figures 2018. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf.
Accessed September 2018.
6 Jonasch, E., Gao, J.,
Rathmell, W. Renal cell carcinoma. BMJ. 2014; 349:g4797.
Decision Resources Report: Renal Cell Carcinoma. October 2014 (internal
data on file).
8 Harshman, L., and Choueiri, T.
Targeting the hepatocyte growth factor/c-Met signaling pathway in renal
cell carcinoma. Cancer J. 2013; 19:316-323.
Rankin, et al. Direct regulation of GAS6/AXL signaling by HIF promotes
renal metastasis through SRC and MET. Proc Natl Acad Sci USA.
10 Zhou, L., Liu, X-D., Sun, M.,
et al. Targeting MET and AXL overcomes resistance to sunitinib therapy
in renal cell carcinoma. Oncogene. 2016; 35:2687-2697.
Koochekpour, et al. The von Hippel-Lindau tumor suppressor gene inhibits
hepatocyte growth factor/scatter factor-induced invasion and branching
morphogenesis in renal carcinoma cells. Mol Cell Biol. 1999;
12 Takahashi, A., Sasaki, H., Kim, S., et
al. Markedly increased amounts of messenger RNAs for vascular
endothelial growth factor and placenta growth factor in renal cell
carcinoma associated with angiogenesis. Cancer Res. 1994;
13 Nakagawa, M., Emoto, A., Hanada, T.,
Nasu, N., Nomura, Y. Tubulogenesis by microvascular endothelial cells is
mediated by vascular endothelial growth factor (VEGF) in renal cell
carcinoma. Br J Urol. 1997; 79:681-687.
Cancer Incidence and Mortality Worldwide. Liver Cancer. International
Agency for Research on Cancer, GLOBOCAN 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
Accessed September 2018.
15 Mittal S, El-Serag HB.
Epidemiology of HCC: Consider the Population. Journal of
Clinical Gastroenterology. 2013. 47:S2-S6.
Weledji E, Orock G, Ngowe M, NsaghaD. How grim is hepatocellular
carcinoma? Annals of Medicine and Surgery. 2014. 3:71-76.
View source version on businesswire.com: https://www.businesswire.com/news/home/20180907005050/en/
Source: Exelixis, Inc.
EVP, Public Affairs and
Lindsay Treadway, 650-837-7522
Director, Public Affairs and