Usual Adult Dose for Breast Cancer

5.4 mg/kg IV every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity

Comments:

• Administer the first infusion over 90 minutes; administer subsequent infusions over 30 minutes if prior infusions were well tolerated.
• Slow or interrupt the infusion rate if the patient develops infusion-related symptoms.
• Permanently discontinue therapy for severe infusion reactions.

Use: For the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received 2 or more prior anti-HER2-based regimens in the metastatic setting

Renal Dose Adjustments

Mild (CrCl 60 to less than 90 mL/min) or moderate (CrCl 30 to less than 60 mL/min) renal impairment: No adjustment recommended.
Severe (CrCl 15 to less than 30 mL/min) or end stage renal disease (CrCl less than 15 mL/min): Data not available

Liver Dose Adjustments

Mild (total bilirubin less than or equal to ULN and any AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN and any AST): No adjustment recommended.
Moderate (total bilirubin greater than 1.5 to 3 x ULN and any AST) hepatic impairment: No adjustment recommended; however, in patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor, DXd.
Severe (total bilirubin greater than 3 to 10 x ULN and any AST) hepatic impairment: Data not available

Dose Adjustments

DOSE MODIFICATIONS:

• Management of adverse reactions may require temporary interruption, dose reduction, or therapy discontinuation.
• Do not re-escalate the dose of this drug after a dose reduction is made.

DOSE REDUCTION SCHEDULE:

• First dose reduction: 4.4 mg/kg
• Second dose reduction: 3.2 mg/kg
• Requirement for further dose reduction: Discontinue therapy.

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS:

• Asymptomatic ILD/pneumonitis (Grade 1): Interrupt this drug until resolved to Grade 0; if resolved in 28 days or less from date of onset, maintain dose; if resolved in greater than 28 days from date of onset, reduce dose one level; consider corticosteroid treatment as soon as ILD/pneumonitis is suspected.
• Symptomatic ILD/pneumonitis (Grade 2 or greater): Permanently discontinue this drug; initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected.

NEUTROPENIA:

• Grade 3 (less than 0.5 to 1 x 10(9)/L): Interrupt this drug until resolved to Grade 2 or less, then maintain dose.
• Grade 4 (less than 0.5 x 109/L): Interrupt this drug until resolved to Grade 2 or less; reduce dose by one level.

FEBRILE NEUTROPENIA:

• Absolute neutrophil count of less than 1 x 10(9)L and temperature greater than 38.3 C or a sustained temperature of 38C or greater for more than one hour: Interrupt this drug until resolved; reduce dose by one level.

LEFT VENTRICULAR DYSFUNCTION (LVEF):

• LVEF greater than 45% and absolute decrease from baseline is 10% to 20%: Continue therapy with this drug.
• LVEF 40% to 45% and absolute decrease from baseline is 10%: Continue therapy with this drug; repeat LVEF assessment within 3 weeks.
• LVEF 40% to 45% and absolute decrease from baseline is 10% to 20%: Interrupt this drug; repeat LVEF assessment within 3 weeks; if LVEF has not recovered to within 10% from baseline, permanently discontinue this drug; if LVEF recovers to within 10% from baseline, resume therapy at the same dose.
• LVEF less than 40% or absolute decrease from baseline is greater than 20%: Interrupt this drug; repeat LVEF assessment within 3 weeks; if LVEF of less than 40% or absolute decrease from baseline of greater than 20% is confirmed, permanently discontinue this drug.

Symptomatic congestive heart failure (CHF): Permanently discontinue this drug.

Precautions

US BOXED WARNINGS:
INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS:

• ILD and pneumonitis (sometimes fatal) have been reported. Monitor for cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue therapy in patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.

EMBRYOFETAL TOXICITY:

• Exposure to this drug during pregnancy can cause embryofetal harm. Advise patients of these risks and the need for effective contraception.

CONTRAINDICATIONS:

• None

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:

• If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle. Adjust the schedule of administration to maintain a 3-week interval between doses. Administer the infusion at the dose and rate the patient tolerated in the most recent infusion.
• If the prepared infusion solution was stored refrigerated (2C to 8C [36F to 46F]), allow the solution to reach room temperature prior to administration.
• Administer this drug as an IV infusion only with an infusion set made of polyolefin or polybutadiene and a 0.2 or 0.22 micron in-line polyethersulfone (PES) or polysulfone (PS) filter.
• Do not administer as an IV push or bolus.
• Do not mix this drug with other drugs or administer other drugs through the same IV line.

Storage requirements:

• Store vials in a refrigerator at 2C to 8C (36F to 46F) in the original carton to protect from light until time of reconstitution.
• Do not freeze.
• Do not shake the reconstituted or diluted solution.

Reconstitution/preparation techniques:

• Reconstitute and further dilute this drug prior to infusion.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be clear and colorless to light yellow. Do not use if visible particles are observed or if the solution is cloudy or discolored.
• The manufacturer product information should be consulted.

Monitoring:

• Verify pregnancy status in female patients of reproductive potential before treatment initiation.
• If a woman becomes pregnant during treatment, close monitoring of the pregnancy is recommended, especially for oligohydramnios.
• Monitor patients for signs and symptoms of ILD/Pneumonitis such as cough, dyspnea, fever and any new or worsening respiratory symptoms. If suspected, evaluate with radiographic imaging and consider consultation with a pulmonologist.
• Complete blood counts should be monitored prior to treatment initiation and prior to each dose.

Patient advice:

• A women of childbearing potential should use effective contraception during treatment and for at least 7 months following the last dose. Men with female partners of childbearing potential should use effective contraception during treatment and for at least 4 months following the last dose.
• Do not breastfeed during treatment and until 7 months after your last dose.

Frequently asked questions

• Is Enhertu a chemotherapy drug? What's Enhertu used for?