Adult Dosing

Indicated as a single agent for treatment of HER2-positive, metastatic breast cancer in patients who previously received trastuzumab and a taxane, separately or in combination

• 3.6 mg/kg IV infusion q3weeks until disease progression or unacceptable toxicity
• Do not exceed 3.6 mg/kg/dose

Dose adjustments indicated

Dose reduction for adverse events

• First dose reduction: 3 mg/kg
• Second dose reduction: 2.4 mg/kg
• Requirement for further dose reduction: Discontinue treatment

Hepatotoxicity

• AST/ALT >2.5 to = < 5x ULN (Grade 2): Maintain same dose level
• AST/ALT >5 to < =20x ULN (Grade 3): Do not administer until AST/ALT recovers to Grade = <2, and then reduce one dose level
• AST/ALT >20x ULN (Grade 4): Permanently discontinue

Hyperbilirubinemia

• >1.5 to < =3x ULN (Grade 2): Do not administer until total bilirubin recovers to Grade = < 1, and then reduce one dose level
• >3 to < =10x ULN (Grade 3): Do not administer until total bilirubin recovers to Grade = < 1, and then reduce one dose level
• >10x ULN (Grade 4): Permanently discontinue

Left ventricular dysfunction

• Symptomatic CHF: Discontinue therapy
• LVEF (Left ventricular ejection fraction) <40%: Do not administer drug; repeat LVEF assessment within 3 weeks, if <40% confirmed, discontinue drug
• LVEF 40% to =45% and decrease is =10% points from baseline: Do not administer drug; repeat LVEF assessment within 3 weeks, if LVEF has not recovered to within 10% points from baseline, discontinue drug
• LVEF 40% to =45% and decrease is <10% points from baseline: Continue drug and repeat LVEF assessment within 3 weeks
• LVEF >45%: Continue therapy

Thrombocytopenia

• Platelets 25,000/mm³ to = < 50,000/mm³: Do not administer until platelet count recovers to = <Grade 1 (ie, = > 75,000/mm³), and then treat at same dose level
• Platelets <25,000/mm³: Do not administer until platelet count recovers to < = Grade 1 (ie, = > 75,000/mm³), and then reduce one dose level

Pulmonary toxicity

• Permanently discontinue with interstitial lung disease or pneumonitis

Peripheral neuropathy

• Temporarily discontinue for Grade 3 or 4 peripheral neuropathy until resolution to < = Grade 2

Pediatric Dosing

• Safety and efficacy have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Indicated as a single agent for treatment of HER2-positive, metastatic breast cancer in patients who previously received trastuzumab and a taxane, separately or in combination

Note:

• Patient should have either received prior therapy for metastatic disease, or developed disease recurrence during or within 6 months of completing adjuvant therapy

• Hypersensitivity to any of the ingredients of the product

• Do not substitute ado-trastuzumab emtansine for or with trastuzumab
• Hepatotoxicity, liver failure and death have occurred in patients. Monitor hepatic function prior to initiation and prior to each dose. Institute dose modifications or permanently discontinue as appropriate
• Therapy may lead to reductions in left ventricular ejection fraction (LVEF). Assess LVEF prior to initiation. Monitor and withhold dosing or discontinue as appropriate
• Can result in embryo-fetal death or birth defects. Advise women of potential risk to the fetus

Renal Dose Adjustment

• Renal impairment: No dose adjustments

Hepatic Dose Adjustment

• Hepatic impairment: Dose adjustments not defined

• Do not substitute ado-trastuzumab emtansine for or with trastuzumab [US black box warning]
• Hepatotoxicity, liver failure and death have occurred in patients. Monitor hepatic function prior to initiation and prior to each dose. Institute dose modifications or permanently discontinue as appropriate [US black box warning]
• Therapy may lead to reductions in left ventricular ejection fraction (LVEF). Assess LVEF prior to initiation. Monitor and withhold dosing or discontinue as appropriate
• Can result in embryo-fetal death or birth defects. Advise women of potential risk to the fetus [US black box warning]
• Hepatotoxicity, serious hepatobiliary disorders, severe drug-induced liver injury and hepatic encephalopathy have been reported. Monitor serum transaminases and bilirubin prior to initiation of treatment and prior to each dose. Permanently discontinue treatment in patients with serum transaminases > 3 x ULN and concomitant total bilirubin > 2 x ULN
• Patients are at increased risk of developing left ventricular dysfunction. Assess LVEF prior to initiation and at regular intervals (e.g. every three months) during treatment to ensure the LVEF is within the institution’s normal limits.
• If, at routine monitoring, LVEF is < 40%, or is 40% to 45% with a 10% or greater absolute decrease below the pretreatment value, withhold therapy and repeat LVEF assessment within approximately 3 weeks. Permanently discontinue if the LVEF has not improved or has declined further
• Therapy may cause fetal harm when administered to a pregnant woman. Treatment with trastuzumab during pregnancy in the postmarketing setting has resulted in oligohydramnios, fatal pulmonary hypoplasia, skeletal abnormalities and neonatal death
• Interstitial lung disease (ILD), including pneumonitis, some leading to acute respiratory distress syndrome or fatal outcome have been reported. Signs and symptoms include dyspnea, cough, fatigue, and pulmonary infiltrates. Permanently discontinue treatment in patients diagnosed with ILD or pneumonitis
• Infusion-related reactions, characterized by flushing, chills, pyrexia, dyspnea, hypotension, wheezing, bronchospasm, or tachycardia have been reported in clinical trials
• Thrombocytopenia, or decreased platelet count has been associated with treatment. Monitor platelet counts prior to initiation of therapy and prior to each dose
• Peripheral neuropathy, mainly as Grade 1 has been reported

Pregnancy Category:D

Breastfeeding: It is unknown whether distributed in human breast milk; a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother

• CNS: Chills, pyrexia, asthenia, fatigue, dizziness, headache, insomnia
• HEMA: Neutropenia, anemia, thrombocytopenia
• CV: Left ventricular dysfunction, hypertension
• EENT: Lacrimation increased, dry eye, vision blurred, conjunctivitis
• RESP: Dyspnea, pneumonitis, cough, epistaxis
• LAB TESTS: Blood alkaline phosphatase increased, increased transaminases, increased bilirubin, increased ast, increased alt, decreased platelet count, decreased hemoglobin, decreased neutrophils
• DERM: Pruritus, rash
• GI: Dyspepsia, stomatitis, dry mouth, abdominal pain, vomiting, diarrhea, constipation, nausea
• METABOLISM: Hypokalemia
• MUSC: Myalgia, arthralgia, musculoskeletal pain
• HYPERSENSITIVITY: Infusion-related reaction, drug hypersensitivity

• HER2-targeted antibody-drug conjugate; binds to sub-domain IV of the HER2 receptor, undergoes receptor-mediated internalization and subsequent lysosomal degradation, resulting in intracellular release of DM1-containing cytotoxic catabolites
• Metabolism: Metabolized mainly by CYP3A4 and CYP3A5
• Excretion: Unknown
• Half-life: 4 days

US Trade Name(s)

• Kadcyla

US Availability

Kadcyla

• PWDR for INJ: 100 mg/vial
• PWDR for INJ: 160 mg/vial

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Hematology/Oncology

Antineoplastics

Monoclonal Antibodies