Drugs List

Therapeutic Indications

Uses

HER2 +ve early breast cancer
Metastatic or locally recurrent unresectable HER2 +ve breast cancer

Early Breast Cancer (EBC)
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 HER2-targeted therapy.

Metastatic Breast Cancer (MBC)
Treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic breast cancer, previously treated with trastuzumab and a taxane, separately or in combination. Patients should have either:

Received prior therapy for locally advanced or metastatic disease
or
Developed disease recurrence during or within six months of completing adjuvant therapy.

Administration

Initial dose: 90 minute intravenous infusion. Patients should be observed during and for at least 90 minutes following the initial infusion.

Subsequent infusions: 30 minute intravenous infusion, if the previous infusion was well tolerated. Patients should be observed for at least 30 minutes following infusions.

Contraindications

Children under 18 years
Left ventricular ejection fraction value of 40% or less
Platelet count below 75 x 10 to the power of 9 / L
Breastfeeding
Pregnancy

Precautions and Warnings

Asian ancestry
Elevated serum transaminases - greater than 2.5 times upper limit of normal
History of anthracycline therapy
Left ventricular ejection fraction value of 45% or less
Patients over 75 years
Platelet count below 100 x 10 to the power of 9 / L at baseline
Risk factors for cardiovascular disorder
Risk of haemorrhage
Hepatic impairment
History of congestive cardiac failure
History of myocardial infarction
Renal impairment - creatinine clearance below 30 ml/minute
Serious cardiac arrhythmias
Serum bilirubin above 1.5 times upper limit of normal
Severe dyspnoea at rest secondary to advanced malignancy
Unstable angina

Advise ability to drive/operate machinery may be affected by side effects
Treatment to be prescribed under the supervision of a specialist
Different preparations of trastuzumab are not interchangeable
Consult local policy on the safe use of anti-cancer drugs
Observe patient for at least 30 minutes following administration
Record name and batch number of administered product
Reduce infusion rate if mild to moderate infusion reaction occurs
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Suspend treatment or reduce rate until infusion reactions resolve
HER2 testing is mandatory prior to initiation of therapy
Monitor cardiac function before and regularly during treatment
Monitor liver function tests at baseline and before each dose
Monitor for signs and symptoms of pneumonitis
Monitor for signs of neurological toxicity
Monitor for signs of portal hypertension
Monitor patient during and for 90 minutes following first administration
Monitor patient for infusion-associated reactions (IARs)
Monitor patients receiving concurrent anticoagulants
Monitor patients receiving concurrent antiplatelets
Monitor platelet count prior to each dose
Advise patient to report any symptoms of interstitial lung disease
Discontinue if nodular regenerative hyperplasia occurs
Discontinue treatment if interstitial lung disease develops
Advise patient to seek advice at first indications of pregnancy
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if hypersensitivity reactions occur
Discontinue if treatment related pneumonitis is diagnosed
Discontinue or review if symptoms of congestive heart failure occur
Discontinue permanently if AST or ALT level exceeds 20 x ULN
Discontinue permanently if life threatening infusion reactions occur
Discontinue treatment if total bilirubin > 10 x ULN
Interrupt therapy if hepatic transaminases > 5 times upper limit of normal
Interrupt treatment if platelet count <50 x 10 to the power of 9/L
Interrupt treatment if severe infusion reaction occurs
Suspend treatment and/or reduce dose if grade 4 thrombocytopenia
Suspend treatment and/or reduce dose if total bilirubin > 3 x ULN
Suspend treatment if LVEF of 40 to 45% & fall of 10% points from baseline
Suspend treatment/reduce dose if grade 3/4 peripheral neuropathy occurs
Female: Contraception required during and for 7 months after treatment
Male: Contraception required during and for 7 months after treatment
Breastfeeding: Do not breastfeed during & for 7 months after treatment
Advise patient of risk of bleeding
Advise patient to report signs / symptoms of infusion related reactions

In order to prevent medication errors it is important to be aware that trastuzumab emtansine (Kadcyla) should not be confused with trastuzumab (Herceptin).

It is important to note that cases of delayed epidermal injury or necrosis following extravasation have been observed within the days to weeks after infusion.

Pregnancy and Lactation

Pregnancy

Trastuzumab emtansine is contraindicated during pregnancy.

The manufacturer suggests trastuzumab emtansine is not recommended for use during pregnancy. If a pregnant woman is treated with trastuzumab emtansine, close monitoring by a multidisciplinary team is desirable. Women who become pregnant should be advised of the possibility of harm to the foetus. There is no data for the use of trastuzumab emtansine in pregnant women.

Cases of oligohydramnios, some associated with fatal pulmonary hypoplasia of the foetus, have been reported in pregnant women receiving trastuzumab.
Animal studies of maytansine a closely related chemical entity of the same class as emtansine, suggest that the microtubule inhibiting cytotoxic component of trastuzumab emtansine, is expected to be teratogenic and potentially embryotoxic.

Briggs suggests trastuzumab does not appear to cause structural anomalies when exposure occurs during organogenesis. HER2 protein expression is high in many embryonic tissues, such as cardiac and neural tissues, and blocking this expression maybe harmful. Trastuzumab has a long elimination half life and could be present in the maternal system for up to 5 months after the last dose.

Lactation

Trastuzumab emtansine is contraindicated during breastfeeding.

The manufacturer recommends that women should discontinue breastfeeding prior to treatment with trastuzumab emtansine and not restart until 7 months after concluding treatment.

It is not known if trastuzumab emtansine is excreted in human milk, however human IgG1 is secreted into human milk, and therefore the potential harm to the infant is unknown.

Side Effects

Abdominal pain
Acute respiratory distress syndrome
Alopecia
Anaemia
Arthralgia
Asthenia
Blurred vision
Chills
Conjunctivitis
Constipation
Cough
Diarrhoea
Dizziness
Dry eyes
Dry mouth
Dysgeusia
Dyspepsia
Dyspnoea
Epistaxis
Extravasation
Fatigue
Gingival bleeding
Haemorrhage
Headache
Hepatic failure
Hepatotoxicity
Hypersensitivity reactions
Hypertension
Hypokalaemia
Increase in alkaline phosphatase
Increase in serum transaminases
Infusion-related symptoms
Insomnia
Interstitial lung disease
Lacrimation
Left ventricular dysfunction
Leucopenia
Memory disturbances
Musculoskeletal pain
Myalgia
Nail disorders
Nausea
Neutropenia
Nodular regenerative hyperplasia
Palmar-Plantar Erythrodysaesthesia syndrome
Peripheral neuropathy
Peripheral oedema
Pneumonitis
Portal hypertension
Pruritus
Pyrexia
Rash
Stomatitis
Thrombocytopenia
Urinary tract infections
Urticaria
Vomiting

Presentation

Parenteral preparations containing trastuzumab emtansine.

Drugs List

Therapeutic Indications

Uses

HER2 +ve early breast cancer
Metastatic or locally recurrent unresectable HER2 +ve breast cancer

Early Breast Cancer (EBC)
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 HER2-targeted therapy.

Metastatic Breast Cancer (MBC)
Treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic breast cancer, previously treated with trastuzumab and a taxane, separately or in combination. Patients should have either:

Received prior therapy for locally advanced or metastatic disease
or
Developed disease recurrence during or within six months of completing adjuvant therapy.

Dosage

Patients treated with trastuzumab emtansine should have HER2 positive tumour status, defined as a score of 3+ by immunohistochemistry (IHC) or a ratio of equal to or greater than 2 by in situ hybridization (ISH) determined by an accurate and validated assay.

Adults

Additional Dosage Information

Administration

Initial dose: 90 minute intravenous infusion. Patients should be observed during and for at least 90 minutes following the initial infusion.

Subsequent infusions: 30 minute intravenous infusion, if the previous infusion was well tolerated. Patients should be observed for at least 30 minutes following infusions.

Contraindications

Children under 18 years
Left ventricular ejection fraction value of 40% or less
Platelet count below 75 x 10 to the power of 9 / L
Breastfeeding
Pregnancy

Precautions and Warnings

Asian ancestry
Elevated serum transaminases - greater than 2.5 times upper limit of normal
History of anthracycline therapy
Left ventricular ejection fraction value of 45% or less
Patients over 75 years
Platelet count below 100 x 10 to the power of 9 / L at baseline
Risk factors for cardiovascular disorder
Risk of haemorrhage
Hepatic impairment
History of congestive cardiac failure
History of myocardial infarction
Renal impairment - creatinine clearance below 30 ml/minute
Serious cardiac arrhythmias
Serum bilirubin above 1.5 times upper limit of normal
Severe dyspnoea at rest secondary to advanced malignancy
Unstable angina

Advise ability to drive/operate machinery may be affected by side effects
Treatment to be prescribed under the supervision of a specialist
Different preparations of trastuzumab are not interchangeable
Consult local policy on the safe use of anti-cancer drugs
Observe patient for at least 30 minutes following administration
Record name and batch number of administered product
Reduce infusion rate if mild to moderate infusion reaction occurs
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Suspend treatment or reduce rate until infusion reactions resolve
HER2 testing is mandatory prior to initiation of therapy
Monitor cardiac function before and regularly during treatment
Monitor liver function tests at baseline and before each dose
Monitor for signs and symptoms of pneumonitis
Monitor for signs of neurological toxicity
Monitor for signs of portal hypertension
Monitor patient during and for 90 minutes following first administration
Monitor patient for infusion-associated reactions (IARs)
Monitor patients receiving concurrent anticoagulants
Monitor patients receiving concurrent antiplatelets
Monitor platelet count prior to each dose
Advise patient to report any symptoms of interstitial lung disease
Discontinue if nodular regenerative hyperplasia occurs
Discontinue treatment if interstitial lung disease develops
Advise patient to seek advice at first indications of pregnancy
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if hypersensitivity reactions occur
Discontinue if treatment related pneumonitis is diagnosed
Discontinue or review if symptoms of congestive heart failure occur
Discontinue permanently if AST or ALT level exceeds 20 x ULN
Discontinue permanently if life threatening infusion reactions occur
Discontinue treatment if total bilirubin > 10 x ULN
Interrupt therapy if hepatic transaminases > 5 times upper limit of normal
Interrupt treatment if platelet count <50 x 10 to the power of 9/L
Interrupt treatment if severe infusion reaction occurs
Suspend treatment and/or reduce dose if grade 4 thrombocytopenia
Suspend treatment and/or reduce dose if total bilirubin > 3 x ULN
Suspend treatment if LVEF of 40 to 45% & fall of 10% points from baseline
Suspend treatment/reduce dose if grade 3/4 peripheral neuropathy occurs
Female: Contraception required during and for 7 months after treatment
Male: Contraception required during and for 7 months after treatment
Breastfeeding: Do not breastfeed during & for 7 months after treatment
Advise patient of risk of bleeding
Advise patient to report signs / symptoms of infusion related reactions

In order to prevent medication errors it is important to be aware that trastuzumab emtansine (Kadcyla) should not be confused with trastuzumab (Herceptin).

It is important to note that cases of delayed epidermal injury or necrosis following extravasation have been observed within the days to weeks after infusion.

Pregnancy and Lactation

Pregnancy

Trastuzumab emtansine is contraindicated during pregnancy.

The manufacturer suggests trastuzumab emtansine is not recommended for use during pregnancy. If a pregnant woman is treated with trastuzumab emtansine, close monitoring by a multidisciplinary team is desirable. Women who become pregnant should be advised of the possibility of harm to the foetus. There is no data for the use of trastuzumab emtansine in pregnant women.

Cases of oligohydramnios, some associated with fatal pulmonary hypoplasia of the foetus, have been reported in pregnant women receiving trastuzumab.
Animal studies of maytansine a closely related chemical entity of the same class as emtansine, suggest that the microtubule inhibiting cytotoxic component of trastuzumab emtansine, is expected to be teratogenic and potentially embryotoxic.

Briggs suggests trastuzumab does not appear to cause structural anomalies when exposure occurs during organogenesis. HER2 protein expression is high in many embryonic tissues, such as cardiac and neural tissues, and blocking this expression maybe harmful. Trastuzumab has a long elimination half life and could be present in the maternal system for up to 5 months after the last dose.

Lactation

Trastuzumab emtansine is contraindicated during breastfeeding.

The manufacturer recommends that women should discontinue breastfeeding prior to treatment with trastuzumab emtansine and not restart until 7 months after concluding treatment.

It is not known if trastuzumab emtansine is excreted in human milk, however human IgG1 is secreted into human milk, and therefore the potential harm to the infant is unknown.

Side Effects

Abdominal pain
Acute respiratory distress syndrome
Alopecia
Anaemia
Arthralgia
Asthenia
Blurred vision
Chills
Conjunctivitis
Constipation
Cough
Diarrhoea
Dizziness
Dry eyes
Dry mouth
Dysgeusia
Dyspepsia
Dyspnoea
Epistaxis
Extravasation
Fatigue
Gingival bleeding
Haemorrhage
Headache
Hepatic failure
Hepatotoxicity
Hypersensitivity reactions
Hypertension
Hypokalaemia
Increase in alkaline phosphatase
Increase in serum transaminases
Infusion-related symptoms
Insomnia
Interstitial lung disease
Lacrimation
Left ventricular dysfunction
Leucopenia
Memory disturbances
Musculoskeletal pain
Myalgia
Nail disorders
Nausea
Neutropenia
Nodular regenerative hyperplasia
Palmar-Plantar Erythrodysaesthesia syndrome
Peripheral neuropathy
Peripheral oedema
Pneumonitis
Portal hypertension
Pruritus
Pyrexia
Rash
Stomatitis
Thrombocytopenia
Urinary tract infections
Urticaria
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: August 2019

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Kadcyla 100mg & 160mg powder for concentrate for solution for infusion. Roche Products Limited. Revised March 2022.

NICE Evidence Services
Available at: www.nice.org.uk
Last accessed: 06 August 2019