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Efficacy data for 2L aRCC CABOMETYX® (cabozantinib) monotherapy

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The only single-agent TKI with superior OS, PFS, and ORR in 2L aRCC1*

*After at least 1 prior anti-angiogenic therapy.1

    METEOR: STUDY DESIGN

    METEOR was a phase 3, randomized, open-label trial vs everolimus in aRCC (N=658).1,2

    1:1 randomization
    Patients had ≥1 prior anti-angiogenic therapy

    CABOMETYX 60 mg QD
    (n=330)

    everolimus 10 mg QD
    (n=328)

    Treatment until disease progression or unacceptable toxicity†

    Primary endpoint
    PFS confirmed by blinded IRRC‡

    Secondary endpoints
    OS
    ORR confirmed by blinded IRRC
    Safety

    The METEOR trial allowed for enrollment of patients who received prior IO therapy.

    †

    Tumor assessments were conducted every 8 weeks for the first 12 months, then every 12 weeks thereafter, per RECIST v1.1. Treatment was continued after disease progression at the discretion of the investigator.

    ‡

    The primary PFS analysis was conducted in the first 375 subjects randomized to treatment. The ITT population included all 658 patients.

    Inclusion criteria1,3,4:

    • Clear-cell component
    • Measurable disease, as defined by RECIST v1.1
    • Radiographic progression within 6 months of enrollment
    • Radiographic progression during treatment with a VEGFR-TKI or within 6 months of last dose
    • No limit to the number of prior therapies
    • Prior treatment with antibodies targeting PD-1/PD-L1/L2 allowed
    • Brain metastases allowed, if adequately treated and stable
    • Karnofsky performance status ≥70%

    Prespecified stratification1,4:

    • MSKCC risk groups: favorable, intermediate, poor
    • Number of prior VEGFR-TKIs: 1, ≥2

    Baseline characteristics

    METEOR evaluated a broad range of patients who had received prior therapy, including prior immunotherapy.

    Baseline Patient Characteristics

     
     

    No. (%)

     

    CABOMETYX
    (n=330)

    everolimus
    (n=328)

    Age (years)

    		  

    Median (IQR)

    63 (56-68)

    62 (55-68)

    Sex

    		  

    Male

    253 (77)

    241 (73)

    Female

    77 (23)

    86 (26)

    Geographic region

    		  

    Europe

    167 (51)

    153 (47)

    North America

    118 (36)

    122 (37)

    Asia-Pacific

    39 (12)

    47 (14)

    Latin America

    6 (2)

    6 (2)

    Race

    		  

    White

    269 (82)

    263 (80)

    Asian

    21 (6)

    26 (8)

    Black

    6 (2)

    3 (<1)

    Other

    19 (6)

    13 (4)

    Not reported

    15 (5)

    22 (7)

    ECOG PS

    		  

    0

    226 (68)

    217 (66)

    1

    104 (32)

    111 (34)

    MSKCC prognostic risk category

    		  

    Favorable

    150 (45)

    150 (46)

    Intermediate

    139 (42)

    135 (41)

    Poor

    41 (12)

    43 (13)

    Metastatic site per IRRC

    		  

    Lung

    204 (62)

    212 (65)

    Liver

    88 (27)

    103 (31)

    Bone

    77 (23)

    65 (20)

    Lymph node

    206 (62)

    199 (61)

    Brain

    2 (<1)

    1 (<1)

    Other

    23 (7)

    21 (6)

    Previous VEGFR-TKIs

    		  

    1

    235 (71)

    229 (70)

    ≥2

    95 (29)

    99 (30)

    Previous systemic therapy

    		  

    Sunitib

    210 (64)

    205 (62)

    Pazapanib

    144 (44)

    136 (41)

    Axitinib

    52 (16)

    55 (17)

    Sorafonib

    21 (6)

    31 (9)

    Bevacizumab

    5 (2)

    11 (3)

    Interleukin 2

    20 (6)

    29 (9)

    Interferon a

    19 (6)

    24 (7)

    Nivolumab§

    17 (5)

    14 (4)

    Radiotherapy

    110 (33)

    108 (33)

    Nephrectomy

    283 (86)

    279 (85)

    §

    One additional patient in the cabozantinib group received prior atezolizumab.

    Data are n (%) or median (IQR).

    METEOR study efficacy data

    Secondary endpoint in METEOR: Median OS1

    21.4
    months
    CABOMETYX
    (n=330)

    VS

    16.5
    months
    everolimus
    (n=328)

    HR=0.66 (95% CI: 0.53-0.83) P=0.0003

    Primary endpoint in METEOR: Median PFS||¶

    7.4
    months
    CABOMETYX
    (n=187)

    VS

    3.8
    months
    everolimus
    (n=188)

    HR=0.58 (95% CI: 0.45-0.74); P<0.0001

    ||

    In the METEOR trial, the primary PFS analysis was conducted in the first 375 subjects randomized to treatment.

    PFS was confirmed by blinded IRRC.

    Secondary endpoint in METEOR: ORR**

    17% 
    CABOMETYX 
    (n=330) 
    (95% CI: 13.0%-22.0%)

    VS

    3% 
    everolimus 
    (n=328) 
    (95% CI: 2.0%-6.0%)

    (P<0.0001); partial responses only

    **ORR was assessed by blinded IRRC using RECIST v1.1.

     
    OTHER RECOMMENDED OPTION†† IN 2L CLEAR-CELL RCC5

    Regardless of prior IO therapy status, cabozantinib is a recommended option.                                                

    ††NCCN Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus (≥85% support of the Panel) that the intervention is appropriate.

    See Monotherapy Safety Data
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    2L=second-line; aRCC=advanced renal cell carcinoma; CI=confidence interval; ECOG PS=Eastern Cooperative Oncology Group performance status; HR=hazard ratio; IO=immuno-oncology; IQR=interquartile range; IRRC=independent radiology review committee; ITT=intent to treat; MSKCC=Memorial Sloan Kettering Cancer Center; NCCN=National Comprehensive Cancer Network; ORR=objective response rate; OS=overall survival; PD-1=programmed cell death protein-1; PD-L1/L2=programmed death ligand-1/2; PFS=progression-free survival; QD=once daily; RECIST=Response Evaluation Criteria in Solid Tumors; TKI=tyrosine kinase inhibitor; VEGFR=vascular endothelial growth factor receptor.

    References:

    1. CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc.
    2. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17(7):917-927. doi:10.1016/S1470-2045(16)30107-3.
    3. Heng DYC, Xie W, Regan MM, 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. J Clin Oncol. 2009;27(34):5794-5799.
    4. Data on file. Exelixis, Inc.
    5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer V.1.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 24, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org.

    IMPORTANT SAFETY INFORMATION

    WARNINGS AND PRECAUTIONS

    Hemorrhage: CABOMETYX can cause severe and fatal hemorrhages. The incidence of Grade 3-5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3-4 hemorrhage and before surgery. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

    Perforations and Fistulas: Fistulas, including fatal cases, and gastrointestinal (GI) perforations, including fatal cases, each occurred in 1% of CABOMETYX patients. Monitor for signs and symptoms, and discontinue CABOMETYX in patients with Grade 4 fistulas or GI perforation.

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

    Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. In CABINET (n=195), hypertension occurred in 65% (26% Grade 3) 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; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with antihypertensive therapy or for hypertensive crisis.

    Diarrhea: CABOMETYX can cause diarrhea and it occurred in 62% (10% Grade 3) of treated patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1; resume at a reduced dose.

    Palmar-Plantar Erythrodysesthesia (PPE): CABOMETYX can cause PPE and it occurred in 45% of treated patients (13% Grade 3). Withhold CABOMETYX until PPE resolves or decreases to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

    Hepatotoxicity: CABOMETYX in combination with nivolumab in RCC can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. Monitor liver enzymes before initiation of treatment and periodically. Consider more frequent monitoring as compared to when the drugs are administered as single agents. Consider withholding CABOMETYX and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life-threatening hepatotoxicity.

    Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.

    Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

    Osteonecrosis of the Jaw (ONJ): CABOMETYX can cause ONJ and it occurred in <1% of treated patients. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution; resume at a reduced dose.

    Impaired Wound Healing: CABOMETYX can cause impaired wound healing. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS): CABOMETYX can cause RPLS. Perform evaluation for RPLS and diagnose by characteristic finding on MRI any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

    Thyroid Dysfunction: CABOMETYX can cause thyroid dysfunction, primarily hypothyroidism, and it occurred in 19% of treated patients (0.4% Grade 3). Assess for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitor for signs and symptoms during treatment.

    Hypocalcemia: CABOMETYX can cause hypocalcemia, with the highest incidence in DTC patients. Based on the safety population, hypocalcemia occurred in 13% of CABOMETYX patients (2% Grade 3 and 1% Grade 4).

    Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume CABOMETYX at a reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.

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

    ADVERSE REACTIONS

    The most common (≥20%) adverse reactions are:

    CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.

    CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

    DRUG INTERACTIONS

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

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

    USE IN SPECIFIC POPULATIONS

    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. Avoid CABOMETYX in patients with severe hepatic impairment.

    Pediatric Use: Physeal widening has been observed in children with open growth plates when treated with CABOMETYX. Physeal and longitudinal growth monitoring is recommended in children (12 years and older) with open growth plates. Consider interrupting or discontinuing CABOMETYX if abnormalities occur. The safety and effectiveness of CABOMETYX in pediatric patients less than 12 years of age have not been established.

    Please see full Prescribing Information.
    You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

    Indications

    CABOMETYX, in combination with nivolumab, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). 

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

    CABOMETYX® (cabozantinib) is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET). 

    CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extrapancreatic neuroendocrine tumors (epNET)​. 

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

    CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.

    CABOMETYX, in combination with nivolumab, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). 

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

    CABOMETYX® (cabozantinib) is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET). 

    CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extrapancreatic neuroendocrine tumors (epNET)​. 

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

    CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.

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