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CABOMETYX® targets MET and AXL in addition to VEGF receptors1


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CABOMETYX® inhibits key receptor tyrosine kinases, including VEGF, MET, and AXL, implicated in tumour growth and angiogenesis, pathologic bone remodelling, drug resistance, and metastatic progression of cancer1.


AXL = growth arrest-specific protein 6 receptor
MET = hepatocyte growth factor receptor
RCC = renal cell carcinoma
VEGF = vascular endothelial growth factor
VEGFR = vascular endothelial growth factor receptor
VHL = Von Hippel-Lindau protein/gene

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CABOMETYX® approval in advanced RCC was based on the METEOR trial.1

A Phase 3 randomised, open-label, study of 658 patients comparing CABOMETYX® with everolimus1,2


View The Lancet Oncology, a New England Journal of Medicine, full publication here



Inclusion criteria2

  • Age ≥ 18 years
  • Advanced or metastatic RCC with a clear-cell component
  • Measurable disease as defined by RECIST version 1.1
  • Prior treatment with ≥ 1 VEGF receptor inhibitor
  • Radiographic progression during treatment or ≤ 6 months after the most recent dose of VEGF receptor inhibitor and ≤ 6 months before randomisation
  • Brain metastases allowed if adequately treated and stable
  • Karnofsky performance score of ≥ 70%
  • Adequate organ and marrow function

Prespecified stratification2

  • Number of prior VEGF receptor inhibitors (1 or ≥ 2)
  • MSKCC risk group (favourable, intermediate or poor)


IRC = Independent Radiology Review Committee; ITT = intent-to-treat; MSKCC = Memorial Sloan Kettering Cancer Center; RECIST = Response Evaluation Criteria in Solid Tumors

 

METEOR trial population: key baseline characteristics1

  The majority of patients received CABOMETYX® in second line1,2

BASELINE DEMOGRAPHIC AND CLINICAL CHARACTERISTICS1*
Overall-Survival Population
 Characteristic Cabozantinib®
(n=330)
Everolimus
(n=328)
Age - yr
Median (range) 63 (32–86) 62 (31–84)
Sex - no. (%)
Male 253 (77) 241 (73)
Female 77 (23) 86 (26)
Not reported 0 1 (<1)
Geographic region - no. (%)
Europe 167 (51) 153 (47)
North America 118 (36) 122 (37)
Asia-Pacific 39 (12) 47 (14)
Latin America 6 (2) 6 (2)
Race — no. (%)
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)
Missing data 0 1 (<1)
ECOG performance status score - no. (%)
0 226 (68) 217 (66)
1 104 (32) 111 (34)
MSKCC risk category - no. (%)§
Favourable 150 (45) 150 (46)
Intermediate 139 (42) 135 (41)
Poor 41 (12) 43 (13)
Prior VEGF receptor inhibitor - no. (%)
1 235 (71) 229 (70)
≥2 95 (29) 99 (30)
Previous systemic therapy in any line - no. (%)
Sunitinib 210 (64) 205 (62)
Pazopanib 144 (44) 136 (41)
Axitinib 52 (16) 55 (17)
Sorafenib 21 (6) 31 (9)
Bevacizumab 5 (2) 11 (3)
Interleukin-2 20 (6) 29 (9)
Interferon alfa 19 (6) 24 (7)
Nivolumab 17 (5) 14 (4)
Radiotherapy — no. (%) 110 (33) 108 (33)
Nephrectomy — no. (%) 282 (85) 279 (85)

* Statistical testing of differences in baseline characteristics between groups was not included in the statistical analysis plan. VEGFR denotes vascular endothelial growth factor receptor.
† Race was self-reported.
‡ Eastern Cooperative Oncology Group (ECOG) performance-status scores range from 0 to 5, with 0 indicating no symptoms, 1 indicating mild symptoms, and higher numbers indicating increasing degrees of disability.
§ The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk category24 was determined by the number of three factors (anemia, hypercalcemia, and poor performance) that were present. Patients with zero factors had a favorable prognosis, patients with one factor had an intermediate prognosis, and patients with two or three factors had a poor prognosis.

1. CABOMETYX® SmPC
2. Choueiri TK, et al. N Engl J Med 2015;373:1814-23
3. Choueiri TK, et al. Lancet Oncol 2016;17:917-27

 

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CABOMETYX® offers a significant overall survival advantage1,2

CABOMETYX® inhibits key receptors including MET and AXL implicated in tumour growth and angiogenesis, pathologic bone remodelling, metastasis, and drug resistance1,2

Recommended dose: 60 mg tablet, once daily1

†PFS analysis population; ‡ITT population; §Partial responses only.

1. CABOMETYX® SmPC
2. Choueiri TK, et al. N Engl J Med 2015;373:1814-23
3. Choueiri TK, et al. Lancet Oncol 2016;17:917-27

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CABOMETYX® significantly delays disease progression1

CABOMETYX® nearly doubled median PFS vs everolimus in the primary population analysis (n=375)1,2*


CABOMETYX® maintained a significant PFS advantage in the overall population analysis (n=658)1,3,*

 


1. CABOMETYX® SmPC
2. Choueiri TK, et al. N Engl J Med 2015;373:1814-23
3. Choueiri TK, et al. Lancet Oncol 2016;17:917-27

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CABOMETYX® offers a significant overall survival advantage1,2

CABOMETYX® extended median OS by almost 5* months vs everolimus in the overall population (n=658)1,2


 

CABOMETYX® resulted in a survival rate of 73% vs 63% for everolimus at 12 months, and 48% vs 31% at 24 months3.


1. CABOMETYX® SmPC
2. Choueiri TK, et al. N Engl J Med 2015;373:1814-23
3. Choueiri TK, et al. Lancet Oncol 2016;17:917-27

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CABOMETYX® significantly and rapidly improves ORR and achieves high tumour control1

The median time to first response with CABOMETYX® is less than 2 months (1.91 months with CABOMETYX® vs 2.14 months with everolimus by IRC)1

CABOMETYX® significantly improved ORR vs everolimus1-3

  • CABOMETYX® induced a partial tumour response in almost a quarter of patients (IR)1,2
  • Almost 9 out of 10 patients achieved a partial response or stable disease with CABOMETYX® (IR)1,2


  • Progressive disease as best response was reported in 12% and 9% of patients receiving CABOMETYX® vs 27% in both of the everolimus analyses (IRC and IR, respectively)1,2

IRC = Independent Radiology Review Committee

1. CABOMETYX® SmPC
2. Choueiri TK, et al. N Engl J Med 2015;373:1814-23
3. Choueiri TK, et al. Lancet Oncol 2016;17:917-27

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CABOMETYX® safety in the METEOR trial1

Adverse events reported as Grade 1–2 in ≥ 10% of patients in either treatment arm (safety population) 1

 

Cabozantinib (n=331) Everolimus (n=322)
Grade 1-2 Grade 3 Grade 4 Grade 1-2 Grade 3 Grade 4
Any adverse event 70 (21) 210 (63) 25 (8) 103 (32) 167 (52) 26 (8)
Diarrhoea 206 (62) 43 (13) 0 85 (26) 7 (2) 0
Fatigue 159 (48) 36 (11) 0 130 (40) 24 (7) 0
Nausea 158 (48) 15 (5) 0 92 (29) 1 (<1) 0
Decreased appetite 146 (44) 10 (3) 0 111 (35) 3 (1) 0
Palmar-plantar erythrodysaesthesia syndrome 115 (35) 27 (8) 0 16 (5) 3 (1) 0
Vomiting 106 (32) 7 (2) 0 44 (14) 3 (1) 0
Weight decreased 105 (32) 9 (3) 0 42 (13) 0 0
Constipation 89 (27) 1 (<1) 0 64 (20) 1 (<1) 0
Dysgeusia 80 (24) 0 0 30 (9) 0 0
Hypothyroidism 76 (23) 0 0 1 (<1) 1 (<1) 0
Hypertension 73 (22) 49 (15) 0 14 (4) 12 (4) 0
Dysphonia 68 (21) 2 (1) 0 16 (5) 0 0
Cough 67 (20) 1 (<1) 0 107 (33) 3 (1) 0
Stomatitis 65 (20) 8 (2) 0 71 (22) 7 (2) 0
Mucosal inflammation 60 (18) 5 (2) 0 64 (20) 10 (3) 1 (<1)
Dyspnoea 56 (17) 10 (3) 0 82 (26) 11 (3) 3 (1)
Aspartate aminotransferase increased 55 (17) 5 (2) 0 19 (6) 1 (<1) 0
Back pain 54 (16) 8 (2) 0 41 (13) 7 (2) 0
Rash 52 (16) 2 (1) 0 92 (29) 2 (1) 0
Asthenia 49 (15) 15 (5) 0 46 (14) 8 (2) 0
Abdominal pain 48 (15) 12 (4) 0 27 (8) 5 (2) 0
Alanine aminotransferase increased 47 (14) 7 (2) 1 (<1) 20 (6) 1 (<1) 0
Pain in extremity 46 (14) 5 (2) 0 31 (10) 1 (<1) 0
Muscle spasms 45 (14) 0 0 17 (5) 0 0
Arthralgia 43 (13) 1 (<1) 0 46 (14) 4 (1) 0
Headache 43 (13) 1 (<1) 0 42 (13) 1 (<1) 0
Anaemia 42 (13) 19 (6) 0 73 (23) 53 (17) 0
Dizziness 41 (12) 1 (<1) 0 21 (7) 0 0
Dyspepsia 40 (12) 1 (<1) 0 15 (5) 0 0
Oedema peripheral 39 (12) 0 0 70 (22) 6 (2) 0
Hypomagnesaemia 38 (12) 6 (2) 10 (3) 5 (2) 0 0
Dry skin 37 (11) 0 0 35 (11) 0 0
Proteinuria 37 (11) 8 (2) 0 28 (9) 2 (1) 0
Flatulence 33 (10) 0 0 7 (2) 0 0
Insomnia 32 (10) 0 0 33 (10) 1 (<1) 0
Pyrexia 31 (9) 3 (1) 0 57 (18) 2 (1) 0
Pruritus 27 (8) 0 0 48 (15) 1 (<1) 0
Blood creatinine increased 17 (5) 1 (< 1) 0 39 (12) 0 0
Hypertriglyceridaemia 17 (5) 4 (1) 0 31 (10) 7 (2) 3 (1)
Hyperglycaemia 15 (5) 2 (1) 1 (< 1) 46 (14) 16 (5) 0
Epistaxis 14 (4) 0 0 46 (14) 0 0
Adverse events that were reported as grade 1–2 in at least 10% of the patients in either study group are shown, irrespective of whether the event was considered by the investigator to be related to the study treatment. All grade 3, 4, and 5 events are listed in the appendix (p 10). One treatment-related death occurred in the cabozantinib group (death; not otherwise specified) and two occurred in the everolimus group (one aspergillus infection and one pneumonia aspiration). Patients are counted once at the highest grade for each preferred term. The severity of adverse events was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).

 

The most frequent adverse events of any grade with CABOMETYX® (experienced by ≥ 25% of patients) were diarrhoea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysaesthesia, hypertension, vomiting, weight loss and constipation1

  • CABOMETYX® dose reduction was used to manage adverse events in 62% of patients1,2
  • Treatment discontinuations due to adverse events were similar for CABOMETYX® and everolimus (12% vs 11%)1,2.

1. CABOMETYX® SmPC
2. Choueiri TK, et al. Lancet Oncol 2016;17:917-27

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CABOMETYX® dosing

Recommended dose of CABOMETYX® is 60 mg orally once-daily1

 


 

  • As most events can occur early in the course of CABOMETYX® therapy, patients should be evaluated closely during the first 8 weeks of treatment to determine if dose modifications are necessary1
  • CABOMETYX® treatment should continue until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs1

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CABOMETYX® administration1

How to take CABOMETYX®1

 


 

Guidance for patients if they miss a dose1

 


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Dose modification

  • Management of suspected adverse reactions may require temporary interruption and / or dose reduction of CABOMETYX® therapy1.
    • Dose interruptions are recommended for the management of Grade 3 or greater toxicities or intolerable Grade 2 toxicities1
    • Dose reductions are recommended for events that, if persistent, could become serious or intolerable1

 

Adverse reaction and severity Treatment modification
Grade 1 and Grade 2 adverse reactions which are tolerable and easily managed Dose adjustment is usually not required. Consider adding supportive care as indicated.
Grade 2 adverse reactions which are intolerable and cannot be managed with a dose reduction or supportive care Interrupt treatment until the adverse reaction resolves to Grade ≤ 1. Add supportive care as indicated. Consider reinitiating at a reduced dose.
Grade 3 adverse reactions (except clinically non-relevant laboratory abnormalities) Interrupt treatment until the adverse reaction resolves to Grade ≤ 1. Add supportive care as indicated. Reinitiate at a reduced dose.
Grade 4 adverse reactions (except clinically non-relevant laboratory abnormalities) Interrupt treatment. Institute appropriate medical care. If adverse reaction resolves to Grade ≤ 1, re-initiate at a reduced dose. If adverse reaction does not resolve, permanently discontinue CABOMETYX®.

 

Note: Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4)

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