Exelixis Announces New Recommendations for CABOMETYX (Cabozantinib) Tablets in Updated National Comprehensive Cancer Network Clinical Practice Guidelines
CABOMETYX recommended for the treatment of previously untreated advanced renal cell carcinoma across all patient risk groups ?
ALAMEDA, California- Exelixis, 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)
- 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.
Exelixis, the?Exelixis?logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks.
_________________________ References: 1?National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Kidney Cancer. Version 1.2019. Updated?September 4, 2018. 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. 2016; 35:591-597. 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. 7?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. 9?Rankin, et al. Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET.?Proc Natl Acad Sci USA. 2014; 111:13373-13378. 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. 11?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; 19:5902?5912. 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; 54:4233-4237. 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. 14?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. 16?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. Investors: Exelixis, Inc. Susan Hubbard, 650-837-8194 EVP, Public Affairs and Investor Relations shubbard@exelixis.com or Media: Exelixis, Inc. Lindsay Treadway, 650-837-7522 Senior Director, Public Affairs and Advocacy Relations ltreadway@exelixis.com