KADCYLA

KADCYLA- ado-trastuzumab emtansine injection, powder, lyophilized, for solution
Genentech, Inc.

WARNING: HEPATOTOXICITY, CARDIAC TOXICITY, EMBRYO-FETAL TOXICITY

  • Hepatotoxicity: Serious hepatotoxicity has been reported, including liver failure and death in patients treated with KADCYLA. Monitor serum transaminases and bilirubin prior to initiation of KADCYLA treatment and prior to each KADCYLA dose. Reduce dose or discontinue KADCYLA as appropriate in cases of increased serum transaminases or total bilirubin. (2.3, 5.1)
  • Cardiac Toxicity: KADCYLA administration may lead to reductions in left ventricular ejection fraction (LVEF). Evaluate left ventricular function in all patients prior to and during treatment with KADCYLA. Withhold treatment for clinically significant decrease in left ventricular function. (2.3, 5.2)
  • Embryo-Fetal Toxicity: Exposure to KADCYLA during pregnancy can result in embryo-fetal harm. Advise patients of these risks and the need for effective contraception. (5.3, 8.1, 8.3)

1 INDICATIONS AND USAGE

1.1 Metastatic Breast Cancer (MBC)

KADCYLA ® , as a single agent, is indicated for the treatment of patients with HER2-positive, metastatic breast cancer 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 six months of completing adjuvant therapy.

Select patients for therapy based on an FDA-approved companion diagnostic for KADCYLA [see Dosage and Administration (2.1) ].

1.2 Early Breast Cancer (EBC)

KADCYLA, as a single agent, is indicated for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab -based treatment.

Select patients for therapy based on an FDA-approved companion diagnostic for KADCYLA [see Dosage and Administration (2.1) ].

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection

Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens [see Indications and Usage (1), Clinical Studies (14)]. Assessment of HER2 protein overexpression and/or HER2 gene amplification should be performed using FDA-approved tests specific for breast cancers by laboratories with demonstrated proficiency. Information on the FDA-approved tests for the detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics.

Improper assay performance, including use of sub-optimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results.

2.2 Recommended Doses and Schedules

Do not substitute trastuzumab for or with KADCYLA.

The recommended dose of KADCYLA is 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle). Do not administer KADCYLA at doses greater than 3.6 mg/kg.

Closely monitor the infusion site for possible subcutaneous infiltration during drug administration [see Warnings and Precautions (5.9)].

First infusion: Administer infusion over 90 minutes. Observe patients during the infusion and for at least 90 minutes following the initial dose for fever, chills, or other infusion-related reactions [see Warnings and Precautions (5.5)].

Subsequent infusions: Administer over 30 minutes if prior infusions were well tolerated. Observe patients during the infusion and for at least 30 minutes after infusion.

Metastatic Breast Cancer (MBC)

Patients with MBC should receive treatment until disease progression or unmanageable toxicity.

Early Breast Cancer (EBC)

Patients with EBC should receive treatment for a total of 14 cycles unless there is disease recurrence or unmanageable toxicity.

2.3 Dose Modifications

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

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.

Slow or interrupt the infusion rate of KADCYLA if the patient develops an infusion-related reaction. Permanently discontinue KADCYLA for life-threatening infusion-related reactions [see Warnings and Precautions (5.5)].

Management of increased serum transaminases, hyperbilirubinemia, left ventricular dysfunction, thrombocytopenia, pulmonary toxicity or peripheral neuropathy may require temporary interruption, dose reduction or treatment discontinuation of KADCYLA as per guidelines provided in Tables 1 and 2.

Table 1 Recommended Dose Reduction Schedule for Adverse Reactions
Dose Reduction Schedule Dose Level
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 treatment
Table 2 Dose Modification Guidelines for KADCYLA
ALT = alanine transaminase; AST = aspartate transaminase, CHF = congestive heart failure, DILI = Drug Induced Liver Injury; LVEF = left ventricular ejection fraction, LVSD = left ventricular systolic dysfunction, TBILI = Total Bilirubin, ULN = upper limit of normal
*
Prior to starting KADCYLA treatment
Dose Modifications for Patients with MBC
Adverse reaction Severity Treatment modification
Increased Transaminase (AST/ALT) Grade 2(> 2.5 to ≤ 5× the ULN) Treat at the same dose level.
Grade 3(> 5 to ≤ 20× the ULN) Do not administer KADCYLA until AST/ALT recovers to Grade ≤ 2, and then reduce one dose level
Grade 4(> 20× the ULN) Discontinue KADCYLA
Hyperbilirubinemia Grade 2(> 1.5 to ≤ 3× the ULN) Do not administer KADCYLA until total bilirubin recovers to Grade ≤ 1, and then treat at the same dose level.
Grade 3(> 3 to ≤ 10× the ULN) Do not administer KADCYLA until total bilirubin recovers to Grade ≤ 1 and then reduce one dose level.
Grade 4(> 10× the ULN) Discontinue KADCYLA
Drug Induced Liver Injury (DILI) Serum transaminases > 3 × ULN and concomitant total bilirubin > 2 × ULN Permanently discontinue KADCYLA in the absence of another likely cause for the elevation of liver enzymes and bilirubin, e.g. liver metastasis or concomitant medication
Nodular Regenerative Hyperplasia (NRH) All Grades Permanently discontinue KADCYLA
Thrombocytopenia Grade 3(25,000 to < 50,000/mm3) Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm3), and then treat at the same dose level
Grade 4(< 25,000/mm3) Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm3), and then reduce one dose level
Left Ventricular Dysfunction Symptomatic CHF Discontinue KADCYLA
LVEF < 40% Do not administer KADCYLARepeat LVEF assessment within 3 weeks. If LVEF < 40% is confirmed, discontinue KADCYLA
LVEF 40% to ≤ 45% and decrease is ≥ 10% points from baseline Do not administer KADCYLARepeat LVEF assessment within 3 weeks. If the LVEF has not recovered to within 10% points from baseline, discontinue KADCYLA
LVEF 40% to ≤ 45% and decrease is < 10% points from baseline Continue treatment with KADCYLA. Repeat LVEF assessment within 3 weeks.
LVEF > 45% Continue treatment with KADCYLA.
Pulmonary Toxicity Interstitial lung disease (ILD) or pneumonitis Permanently discontinue KADCYLA
Peripheral Neuropathy Grade 3-4 Do not administer KADCYLA until resolution Grade ≤ 2
Dose Modification Guidelines for EBC
Adverse reaction Severity Treatment modification
Increased Alanine Transaminase (ALT) Grade 2-3(> 3.0 to ≤ 20 × ULN on day of scheduled treatment) Do not administer KADCYLA until ALT recovers to Grade ≤ 1, and then reduce one dose level
Grade 4(> 20 × ULN at any time) Discontinue KADCYLA
Increased Aspartate Transaminase (AST) Grade 2(> 3.0 to ≤ 5 × ULN on day of scheduled treatment) Do not administer KADCYLA until AST recovers to Grade ≤ 1, and then treat at the same dose level
Grade 3(> 5 to ≤ 20 × ULN on day of scheduled treatment) Do not administer KADCYLA until AST recovers to Grade ≤ 1, and then reduce one dose level
Grade 4(> 20 × ULN at any time) Discontinue KADCYLA
Hyperbilirubinemia TBILI> 1.0 to ≤ 2.0 × the ULN on day of scheduled treatment Do not administer KADCYLA until total bilirubin recovers to ≤ 1.0 × ULN, and then reduce one dose level
TBILI> 2 × ULN at any time Discontinue KADCYLA
Nodular Regenerative Hyperplasia (NRH) All Grades Permanently discontinue KADCYLA
Thrombocytopenia Grade 2-3 on day of scheduled treatment(25,000 to < 75,000/mm3) Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm3), and then treat at the same dose level. If a patient requires 2 delays due to thrombocytopenia, consider reducing dose by one level.
Grade 4 at any time< 25,000/mm3 Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm3), and then reduce one dose level.
Left Ventricular Dysfunction LVEF < 45% Do not administer KADCYLARepeat LVEF assessment within 3 weeks. If LVEF < 45% is confirmed, discontinue KADCYLA.
LVEF 45% to < 50% and decrease is ≥ 10% points from baseline * Do not administer KADCYLARepeat LVEF assessment within 3 weeks. If the LVEF remains < 50% and has not recovered to < 10% points from baseline, discontinue KADCYLA.
LVEF 45% to < 50% and decrease is < 10% points from baseline * Continue treatment with KADCYLA.Repeat LVEF assessment within 3 weeks.
LVEF ≥ 50% Continue treatment with KADCYLA.
Heart Failure Symptomatic CHF,Grade 3-4 LVSD or Grade 3-4 heart failure, orGrade 2 heart failureaccompanied by LVEF < 45% Discontinue KADCYLA
Peripheral Neuropathy Grade 3-4 Do not administer KADCYLA until resolution Grade ≤ 2
Pulmonary Toxicity Interstitial lung disease (ILD) or pneumonitis Permanently discontinue KADCYLA
Radiotherapy-Related Pneumonitis Grade 2 Discontinue KADCYLA if not resolving with standard treatment
Grade 3-4 Discontinue KADCYLA

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.