Cabometyx

Cabozantinib

Monotherapy for advanced renal cell carcinoma (RCC) as 1st-line treatment of adults w/ intermediate or poor risk; in adults following prior vascular endothelial growth factor-targeted therapy. In combination w/ nivolumab for 1st-line treatment of advanced RCC in adults. Monotherapy for hepatocellular carcinoma (HCC) in adults who have previously been treated w/ sorafenib. Monotherapy for locally advanced or metastatic differentiated thyroid carcinoma (DTC), refractory or not eligible to radioactive iodine in adults who have progressed during or after prior systemic therapy.

RCC, HCC & DTC Monotherapy: 60 mg once daily. May reduce dose to 40 mg daily then 20 mg daily if necessary. 1st-line advanced RCC Combination therapy: 40 mg once daily w/ nivolumab IV at either 240 mg every 2 wk or 480 mg every 4 wk. May reduce dose to 20 mg once daily then 20 mg every other day.

Should be taken on an empty stomach: Swallow whole, do not crush.

Hypersensitivity.

Closely evaluate patient during the 1st 8 wk of treatment to determine if dose modifications are warranted. Risk of hepatic toxicity; hepatic encephalopathy; serious GI perforations & fistulas; GI disorders (ie, diarrhoea, nausea/vomiting, decreased appetite, stomatitis/oral pain); thromboembolic events; severe haemorrhage; thrombocytopenia & decreased platelets; wound complications; HTN, including hypertensive crisis; osteonecrosis of the jaw; palmar-plantar erythrodysaesthesia syndrome; proteinuria; posterior reversible encephalopathy syndrome. Perform LFTs (eg, ALT, AST & bilirubin) before initiation of treatment; closely monitor during treatment. May promote formation of aneurysms &/or artery dissections in patients w/ or w/o HTN. Periodically monitor thyroid function throughout treatment. Increased incidence of electrolyte abnormalities (including hypo- & hyperkalaemia, hypomagnesaemia, hypocalcaemia, hyponatremia). Caution in patients w/ history of QT interval prolongation, patients who are taking antiarrhythmics, or patients w/ relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances. Stop treatment at least 28 days prior to scheduled surgery, including dental surgery or invasive dental procedures, if possible. Caution when concomitantly administered w/ strong CYP3A4 inhibitors, P-gp substrates, MRP2 inhibitors. Avoid chronic administration of strong CYP3A4 inducers w/ cabozantinib. Not to be taken by patients w/ rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Minor influence on the ability to drive & use machines. Close monitoring is advised in patients w/ mild or moderate hepatic impairment. Caution in patients w/ mild or moderate renal impairment. Not recommended for use in patients w/ severe renal or hepatic impairment. Limited data in patients w/ cardiac impairment. Women of childbearing potential must avoid pregnancy during therapy. Effective methods of contraception should be used by male & female patients & their partners during therapy, & for at least 4 mth after completing therapy. OCs should be used together w/ another contraceptive method eg, barrier method. Should not be used during pregnancy unless clinical condition requires. Discontinue breast-feeding during treatment & for at least 4 mth after completing therapy. Male & female fertility may be compromised by cabozantinib treatment. Safety & efficacy have not been established in childn & adolescents <18 yr.

Anaemia, thrombocytopenia; hypothyroidism; decreased appetite, hypomagnesaemia, hypokalaemia, hypoalbuminaemia; dysgeusia, headache, dizziness; HTN, haemorrhage; dysphonia, dyspnoea, cough; diarrhoea, nausea, vomiting, stomatitis, constipation, abdominal pain, dyspepsia; palmar-plantar erythrodysaesthesia syndrome, rash; pain in extremity; fatigue, mucosal inflammation, asthenia, peripheral oedema; decreased wt, increased serum ALT, increased AST. Abscess; neutropenia, lymphopenia; dehydration, hypophosphataemia, hyponatraemia, hypocalcaemia, hyperkalaemia, hyperbilirubinemia, hyperglycaemia, hypoglycaemia; peripheral neuropathy; tinnitus; venous thrombosis; pulmonary embolism; GI perforation, pancreatitis, fistula, GERD, haemorrhoids, oral pain, dry mouth, dysphagia; hepatic encephalopathy; pruritus, alopecia, dry skin, dermatitis acneiform, hair colour change, hyperkeratosis, erythema; muscle spasms, arthralgia; proteinuria; increased blood ALP, GGT, blood creatinine, amylase, lipase, blood cholesterol & blood triglycerides.

Decreased clearance & increased exposure (AUC) w/ strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice). Increased clearance & decreased exposure (AUC) w/ strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampicin, phenobarb or herbal prep containing St. John's Wort). Possible increased plasma conc w/ MRP2 inhibitors. Potentially decreased exposure w/ bile salt-sequestering agents (eg, cholestyramine, cholestagel). Interaction w/ warfarin is possible; monitor INR values. Unchanged effect of contraceptive steroids may not be guaranteed; additional contraceptive method (eg, barrier method) is recommended. Potential to increase plasma conc of P-gp substrates (eg, fexofenadine, aliskiren, ambrisentan, dabigatran etexilate, digoxin, colchicine, maraviroc, posaconazole, ranolazine, saxagliptin, sitagliptin, talinolol, tolvaptan).

Targeted Cancer Therapy

L01EX07 - cabozantinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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