Active Ingredient: Trastuzumab emtansine
Trastuzumab emtansine, as a single agent, is indicated for the adjuvant treatment of adult patients with HER2-positive early breast cancer who have residual invasive disease, in the breast and/or lymph nodes, after neoadjuvant taxane-based and HER2-targeted therapy.
Trastuzumab emtansine, as a single agent, is indicated for the treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:
For this indication, competent medicine agencies globally authorize below treatments:
Intravenous
3.6 - 3.6 mg per kg of body weight
From 3.6 To 3.6 mg per kg of body weight once every 21 day(s)
The recommended dose of trastuzumab emtansine is 3.6 mg/kg bodyweight administered as an intravenous infusion every 3 weeks (21-day cycle).
The initial dose should be administered as a 90 minute intravenous infusion. Patients should be observed during the infusion and for at least 90 minutes following the initial infusion for fever, chills, or other infusion-related reactions. The infusion site should be closely monitored for possible subcutaneous infiltration during administration.
If the prior infusion was well tolerated, subsequent doses of trastuzumab emtansine may be administered as 30 minute infusions. Patients should be observed during the infusion and for at least 30 minutes after infusion.
The infusion rate of trastuzumab emtansine should be slowed or interrupted if the patient develops infusion-related symptoms.
Patients should receive treatment for a total of 14 cycles unless there is disease recurrence or unmanageable toxicity.
Patients should receive treatment until disease progression or unmanageable toxicity.
Management of symptomatic adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of trastuzumab emtansine as per guidelines provided in text and the following tables.
Trastuzumab emtansine dose should not be re-escalated after a dose reduction is made.
Dose reduction schedule:
| Dose reduction schedule (Starting dose is 3.6 mg/kg) | Dose to be administered |
|---|---|
| First dose reduction | 3 mg/kg |
| Second dose reduction | 2.4 mg/kg |
| Requirement for further dose reduction | Discontinue treatment |
If a planned dose is missed, it should be administered as soon as possible; without waiting until the next planned cycle. The schedule of administration should be adjusted to maintain a 3-week interval between doses. The next dose should be administered in accordance with the dosing recommendations above.
Dose Modification Guidelines:
| Dose Modifications for Patients with EBC | ||
|---|---|---|
| Adverse reaction | Severity | Treatment modification |
| Thrombocytopenia | Grade 2-3 on day of scheduled treatment (25,000 to <75,000/mm3) | Do not administer trastuzumab emtansine 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 trastuzumab emtansine until platelet count recovers to ≤ Grade 1 (≥75,000/mm3), and then reduce one dose level. | |
| Increased Alanine Transaminase (ALT) | Grade 2-3 (>3.0 to ≤20 x ULN on day of scheduled treatment) | Do not administer trastuzumab emtansine until ALT recovers to Grade ≤1, and then reduce one dose level |
| Grade 4 (>20 x ULN at any time) | Discontinue trastuzumab emtansine | |
| Increased Aspartate Transaminase (AST) | Grade 2 (>3.0 to ≤ 5 x ULN on day of scheduled treatment) | Do not administer trastuzumab emtansine until AST recovers to Grade ≤1, and then treat at the same dose level |
| Grade 3 (>5 to ≤20 x ULN on day of scheduled treatment) | Do not administer trastuzumab emtansine until AST recovers to Grade ≤1, and then reduce one dose level | |
| Grade 4 (>20 x ULN at any time) | Discontinue trastuzumab emtansine | |
| Hyperbilirubinemia | TBILI >1.0 to ≤2.0 x the ULN on day of scheduled treatment | Do not administer trastuzumab emtansine until total bilirubin recovers to ≤1.0 × ULN, and then reduce one dose level |
| TBILI >2 x ULN at any time | Discontinue trastuzumab emtansine | |
| Drug Induced Liver Injury (DILI) | Serum transaminases >3 x ULN and concomitant total bilirubin >2 x ULN | Permanently discontinue trastuzumab emtansine 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 trastuzumab emtansine |
| Peripheral Neuropathy | Grade 3-4 | Do not administer trastuzumab emtansine until resolution Grade 2 |
| Left Ventricular Dysfunction | LVEF <45% | Do not administer trastuzumab emtansine. Repeat LVEF assessment within 3 weeks. If LVEF <45% is confirmed, discontinue trastuzumab emtansine |
| LVEF 45% to <50% and decrease is ≥10% points from baseline* | Do not administer trastuzumab emtansine. Repeat LVEF assessment within 3 weeks. If the LVEF remains <50% and has not recovered to <10% points from baseline, discontinue trastuzumab emtansine. | |
| LVEF 45% to <50% and decrease is <10% points from baseline* | Continue treatment with trastuzumab emtansine. Repeat LVEF assessment within 3 weeks. | |
| LVEF ≥50% | Continue treatment with trastuzumab emtansine | |
| Heart Failure | Symptomatic CHF, Grade 3-4 LVSD or Grade 3-4 heart failure, or Grade 2 heart failure accompanied by LVEF <45% | Discontinue trastuzumab emtansine |
| Pulmonary Toxicity | Interstitial lung disease (ILD) or pneumonitis | Permanently discontinue trastuzumab emtansine |
| Radiotherapy-Related Pneumonitis | Grade 2 | Discontinue trastuzumab emtansine if not resolving with standard treatment |
| Grade 3-4 | Discontinue trastuzumab emtansine | |
| Dose Modifications for Patients with MBC | ||
| Adverse reaction | Severity | Treatment modification |
| Thrombocytopenia | Grade 3 (25,000 to <50,000/mm3) | Do not administer trastuzumab emtansine 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 trastuzumab emtansine until platelet count recovers to ≤ Grade 1 (≥75,000/mm3), and then reduce one dose level | |
| Increased Transaminase (AST/ALT) | Grade 2 (>2.5 to ≤5 x the ULN) | Treat at the same dose level |
| Grade 3 (>5 to ≤20 x the ULN) | Do not administer trastuzumab emtansine until AST/ALT recovers to Grade ≤2, and then reduce one dose level | |
| Grade 4 (>20 x the ULN) | Discontinue trastuzumab emtansine | |
| Hyperbilirubinemia | Grade 2 (>1.5 to ≤3 x the ULN) | Do not administer trastuzumab emtansine until total bilirubin recovers to Grade ≤1, and then treat at the same dose level |
| Grade 3 (>3 to ≤10 x the ULN) | Do not administer trastuzumab emtansine until total bilirubin recovers to Grade ≤1 and then reduce one dose level | |
| Grade 4 (>10 x the ULN) | Discontinue trastuzumab emtansine | |
| Drug Induced Liver Injury (DILI) | Serum transaminases >3 x ULN and concomitant total bilirubin >2 x ULN | Permanently discontinue trastuzumab emtansine in the absence of another likely cause for the elevation of liver enzymes and bilirubin, e.g. liver metastasis or concomitant medication |
| Left Ventricular Dysfunction | Symptomatic CHF | Discontinue trastuzumab emtansine |
| LVEF <40% | Do not administer trastuzumab emtansine. Repeat LVEF assessment within 3 weeks. If LVEF <40% is confirmed, discontinue trastuzumab emtansine | |
| LVEF 40% to ≤45% and decrease is ≥10% points from baseline | Do not administer trastuzumab emtansine. Repeat LVEF assessment within 3 weeks. If the LVEF has not recovered to within 10% points from baseline, discontinue trastuzumab emtansine | |
| LVEF 40% to ≤45% and decrease is <10% points from baseline | Continue treatment with trastuzumab emtansine. Repeat LVEF assessment within 3 weeks | |
| LVEF >45% | Continue treatment with trastuzumab emtansine | |
ALT = alanine transaminase; AST = aspartate transaminase, CHF = congestive heart failure, LVEF = left ventricular ejection fraction, LVSD = left ventricular systolic dysfunction, TBILI = Total Bilirubin, ULN = upper limit of normal
* Prior to starting trastuzumab emtansine treatment.
Liability Disclaimer : RxReasoner has utilized reasonable care in providing content and services that are accurate, complete and up to date. However, RxReasoner does not accept any responsibility or liability about it. The content and services of RxReasoner are for informational purposes only and they are not intended to be a substitute for the knowledge, expertise, skill, and judgment of physicians, pharmacists, nurses, or other healthcare professionals involved in patient care. RxReasoner offers no medical advice. Users are responsible for the use of the provided content. A shown indication or treatment should not be construed to indicate that the medication is safe, appropriate, or effective in any given patient or under any particular circumstances. The absence of an indication or treatment should not roule out the existence of other appropriate medications. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition or medicament. RxReasoner is not liable for any damages allegedly sustained arising out of the use of its content and services.
