CABOMETYX targets 3 key drivers of aRCC and HCC tumorigenesis—MET, AXL, and VEGFR1

  • In RCC and HCC tumor cells and cells of the tumor microenvironment, MET, AXL, and VEGF are overexpressed2-8
  • These receptors are involved in normal and pathologic processes such as tumor angiogenesis, invasiveness, metastasis, and immunomodulation of the tumor microenvironment1,3,7,9-15

Mechanism of action shown is based on in vitro biochemical and/or cellular assays.1

CABOMETYX is the only approved TKI that goes beyond the VEGF pathway to target MET and AXL


aRCC=advanced renal cell carcinoma; AXL=growth arrest-specific protein 6 receptor; HCC=hepatocellular carcinoma; MET=hepatocyte growth factor receptor; RCC=renal cell carcinoma; TKI=tyrosine kinase inhibitor; VEGF=vascular endothelial growth factor; VEGFR=vascular endothelial growth factor receptor.



CABOMETYX® (cabozantinib) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC).

CABOMETYX® (cabozantinib) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.



Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: GastrointestinaI (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Proteinuria: Proteinuria occurred in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 28 days prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution.

Wound Complications: Wound complications were reported with CABOMETYX. Stop CABOMETYX at least 28 days prior to scheduled surgery. Resume CABOMETYX after surgery based on clinical judgment of adequate wound healing. Withhold CABOMETYX in patients with dehiscence or wound healing complications requiring medical intervention.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.


The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, and vomiting.


Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.


Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with 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.

References: 1. CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc, 2019. 2. Rankin EB, Fuh KC, Castellini L, et al. Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET. Proc Natl Acad Sci USA. 2014;111(37):13373-13378. 3. 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(21):2687-2697. doi:10.1038/onc.2015.343. 4. Kwilas AR, Ardiani A, Donahue RN, et al. Dual effects of a targeted small-molecule inhibitor (cabozantinib) on immune-mediated killing of tumor cells and immune tumor microenvironment permissiveness when combined with a cancer vaccine. J Transl Med. 2014;12:294. 5. Tannir NM, Schwab G, Grunwald V. Cabozantinib: an active novel multikinase inhibitor in renal cell carcinoma. Curr Oncol Rep. 2017;19(2):1-8. doi:10.1007/s11912-017-0566-9. 6. Goyal L, Muzumdar MD, Zhu AX. Targeting the HGF/c-MET pathway in hepatocellular carcinoma. Clin Cancer Res. 2013;19(9):2310-2318. doi:10.1158/1078-0432.CCR-12-2791. 7. Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54-63. doi:10.1056/NEJMoa1717002. 8. Graham DK, Deryckere D, Davies KD, Earp HS. The TAM family: phosphatidylserine-sensing receptor tyrosine kinases gone awry in cancer. Nat Rev Cancer. 2014;14(12):769-785. doi:10.1038/nrc3847. 9. Bukowski RM. Third generation tyrosine kinase inhibitors and their development in advanced renal cell carcinoma. Front Oncol. 2012;2(13):1-10. 10. Koochekpour S, Jeffers M, Wang PH, 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(9):5902-5912. 11. Aguilera TA, Giaccia AJ. Molecular pathways: oncologic pathways and their role in T-cell exclusion and immune evasion—a new role for the AXL receptor tyrosine kinase. Clin Cancer Res. 2017;23(12):2928-2933. doi:10.1158/1078-0432.ccr-17-0189. 12. Aguilera TA, Rafat M, Castellini L, et al. Reprogramming the immunological microenvironment through radiation and targeting AXL. Nat Commun. 2016;7(13898):1-14. doi:10.1038/ncomms13898. 13. Ilangumaran S, Villalobos-Hernandez A, Bobbala D, Ramanathan S. The hepatocyte growth factor (HGF)-MET receptor tyrosine kinase signaling pathway: diverse roles in modulating immune cell functions. Cytokine. 2016;82:125-139. doi:10.1016/j.cyto.2015.12.013. 14. Hubel J, Hieronymus T. HGF/MET-signaling contributes to immune regulation by modulating tolerogenic and motogenic properties of dendritic cells. Biomedicines. 2015;3(1):138-148. doi:10.3390/biomedicines3010138. 15. Yang J, Yan J, Liu B. Targeting VEGF/VEGFR to modulate antitumor immunity. Front Immunol. 2018;9:1-9. doi:10.3389/fimmu.2018.00978.

CABOMETYX now #1 TKI in new prescriptions for aRCC
CABOMETYX now approved in treatment of HCC