Usual Adult Dose for Breast Cancer

3.6 mg/kg IV every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity
Maximum dose: 3.6 mg/kg IV every 3 weeks

Comments:

• Administer the first infusion over 90 minutes. Subsequent infusions may be administered over 30 minutes as tolerated.
• Observe patients during and for at least 90 minutes following the initial dose for fever, chills, or other infusion-related reactions.
• Patients should have a HER2 positive tumor status confirmed prior to starting therapy.
• Do not substitute trastuzumab emtansine for or with trastuzumab.
• If a planned dose is delayed or missed, it should be administered as soon as possible; do not wait until the next planned cycle.

Use: As a single agent, for HER2-positive, metastatic breast cancer in patients who previously received trastuzumab and a taxane, separately or in combination; patients should have either:

• Received prior therapy for metastatic disease

OR

• Developed disease recurrence during or within 6 months of completing adjuvant therapy

Renal Dose Adjustments

Mild to moderate renal dysfunction (CrCl 30 to 89 mL/min): No adjustment recommended.
Severe renal dysfunction (CrCl less than 30 mL/min): Data not available

Liver Dose Adjustments

Serum Transaminase (AST/ALT) Increases:

• Grade 2 increase (greater than 2.5 to less than or equal to 5 times upper limit of normal [ULN]): No adjustment recommended.
• Grade 3 increase (greater than 5 to less than or equal to 20 x ULN): Hold further doses until AST/ALT recovers to Grade 2 or less and then reduce dose one level.
• Grade 4 increase (greater than 20 times ULN): Permanently discontinue therapy.

Hyperbilirubinemia:

• Grade 2 (greater than 1.5 to less than or equal to 3 x ULN): Hold therapy until total bilirubin is Grade 1 or less and then resume therapy at same dose level.
• Grade 3 (greater than 3 to less than or equal to 10 x ULN): Hold therapy until total bilirubin is Grade 1 or less and then reduce one dose level.
• Grade 4 (greater than 10 x ULN): Permanently discontinue therapy.

Permanently discontinue therapy for concomitant serum transaminases greater than 3 x ULN and total bilirubin greater than 2 x ULN or for nodular regenerative hyperplasia (NRH).

Dose Adjustments

NOTE: Do not re-escalate the dose after a dose reduction is made.

Dose Reductions for Adverse Events:

• Starting dose: 3.6 mg/kg
• First dose reduction: 3 mg/kg
• Second dose reduction: 2.4 mg/kg
• Requirement for further dose reduction: Discontinue therapy.

Left Ventricular Dysfunction (LEVF):

• Symptomatic CHF: Discontinue therapy.
• LVEF less than 40%: Withhold therapy and repeat LVEF assessment within 3 weeks. If LVEF less than 40% is confirmed, discontinue therapy.
• LVEF 40% to less than or equal to 45% and decrease is 10% or greater points from baseline: Withhold therapy and repeat LVEF assessment within 3 weeks. If the LVEF has not recovered to within 10% points of baseline, discontinue therapy.
• LVEF 40% to less than or equal to 45% and decrease is less than 10% points from baseline: Continue therapy and repeat LVEF assessment within 3 weeks.
• LVEF greater than 45%: Continue therapy.

Thrombocytopenia:

• Platelet count of 25,000/mm3 to less than 50,000/mm3: Withhold therapy until platelet count recovers to less than or equal to Grade 1 (greater than or equal to 75,000/mm3) and then resume therapy at same dose level.
• Platelet count less than 25,000/mm3: Withhold therapy until platelet count recovers to less than or equal to Grade 1 (greater than or equal to 75,000/mm3) and then reduce one dose level.

Pulmonary Toxicity:

• Permanently discontinue therapy in patients with interstitial lung disease (ILD) or pneumonitis.

Peripheral Neuropathy:

• Withhold therapy in patients experiencing Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.

Precautions

US BOXED WARNINGS:
WARNING: Do not substitute ado-trastuzumab emtansine for or with trastuzumab.
HEPATOTOXICITY/CARDIAC TOXICITY/EMBRYOFETAL TOXICITY:

• Hepatotoxicity has been reported, including liver failure and death. Monitor serum transaminases and bilirubin prior to initiation of therapy and prior to each dose. Reduce dose or discontinue therapy if necessary in cases of increased serum transaminases or total bilirubin.
• This drug can cause reductions in left ventricular ejection fraction (LVEF). Evaluate left ventricular function in all patients prior to and during therapy. Withhold therapy for decrease in left ventricular function.
• This drug can cause embryofetal harm when administered to a pregnant woman. Advise patients of these risks and the need for effective contraception.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Closely monitor the infusion site for possible subcutaneous infiltration during drug administration.
• Administer the first infusion over 90 minutes. Patients should be observed during the infusion and for at least 90 minutes following the initial dose for fever, chills, or other infusion related reactions.
• Administer subsequent infusions over 30 minutes if prior infusions were well tolerated. Patients should be observed during the infusion and for at least 30 minutes after infusion.
• The infusion rate should be slowed or interrupted if the patient develops an infusion related reaction.
• If a planned dose is delayed or missed, it should be administered as soon as possible; do not wait until the next planned cycle. The schedule of administration should be adjusted to maintain a 3-week interval between doses. The infusion may be administered at the dose and rate the patient tolerated in the most recent infusion.

Storage requirements: Store vials in a refrigerator at 36F to 46F until time of reconstitution. Do not freeze or shake.

Reconstitution/preparation techniques: The manufacturer product information should be consulted.

General:

• To prevent medication errors check the vial labels to ensure that the drug being prepared and administered is trastuzumab emtansine and not trastuzumab.
• Follow procedures for proper handling and disposal of anticancer drugs.

Frequently asked questions

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