Glossary

Resources for breast cancer nurses

Information for nurses and their HER2-positive (HER2+) breast cancer patients

Treating HER2+ breast cancer is no simple task, and a little extra information can make a difference. These materials, provided by Genentech, discuss topics that apply to different steps along the breast cancer journey.

Download these helpful resources or request a Genentech Nurse Educator for more information.

The information provided here does not replace the advice of a medical team. Genentech does not provide medical advice regarding medical conditions or treatment. Your healthcare team should always be your primary source of information. These resources cannot replace information from your doctor and healthcare team.

Select from the list of topics below to view and download resources.

Indications

Adjuvant Breast Cancer

Herceptin® (trastuzumab) is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature*) breast cancer:

  • As part of a treatment regimen containing doxorubicin, cyclophosphamide and either paclitaxel or docetaxel
  • With docetaxel and carboplatin
  • As a single agent following multi-modality anthracycline-based therapy

Select patients for therapy based on an FDA-approved companion diagnostic for Herceptin

*High-risk is defined as ER/PR-positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3.

 

Metastatic Breast Cancer

Herceptin is indicated:

  • In combination with paclitaxel for the first line treatment of HER2-overexpressing metastatic breast cancer
  • As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease

Select patients for therapy based on an FDA-approved companion diagnostic for Herceptin

Boxed WARNINGS and Additional Important Safety Information

Cardiomyopathy

  • Herceptin administration can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving Herceptin with anthracycline-containing chemotherapy regimens.
  • Evaluate left ventricular function in all patients prior to and during treatment with Herceptin. Discontinue Herceptin treatment in patients receiving adjuvant therapy and withhold Herceptin in patients with metastatic disease for clinically significant decrease in left ventricular function

Infusion Reactions; Pulmonary Toxicity

  • Herceptin administration can result in serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during or within 24 hours of Herceptin administration.  Interrupt Herceptin infusion for dyspnea or clinically significant hypotension. Monitor patients until symptoms completely resolve. Discontinue Herceptin for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome

Embryo-Fetal Toxicity

  • Exposure to Herceptin during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception

Cardiomyopathy

  • Herceptin administration can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving Herceptin with anthracycline-containing chemotherapy regimens. In a pivotal adjuvant trial, one patient who developed CHF died of cardiomyopathy
  • Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death
  • Herceptin can also cause asymptomatic decline in LVEF
  • Discontinue Herceptin treatment in patients receiving adjuvant therapy and withhold Herceptin in patients with metastatic disease for clinically significant decrease in left ventricular function

Cardiac Monitoring

  • Evaluate cardiac function prior to and during treatment. For adjuvant therapy, also evaluate cardiac function after completion of Herceptin
  • Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan
  • Monitor frequently for decreased left ventricular function during and after Herceptin treatment
  • Monitor more frequently if Herceptin is withheld for significant left ventricular cardiac dysfunction

Infusion Reactions

  • Herceptin administration can result in serious and fatal infusion reactions
  • Symptoms usually occur during or within 24 hours of Herceptin administration
  • Interrupt Herceptin infusion for dyspnea or clinically significant hypotension
  • Monitor patients until symptoms completely resolve
  • Discontinue Herceptin for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Strongly consider permanent discontinuation in all patients with severe infusion reactions
  • Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion include nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia

Embryo-Fetal Toxicity

  • Exposure to Herceptin during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception
  • Verify the pregnancy status of females of reproductive potential prior to the initiation of Herceptin
  • Advise pregnant women and females of reproductive potential that exposure to Herceptin during pregnancy or within 7 months prior to conception can result in fetal harm
  • Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of Herceptin
  • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Herceptin treatment and any potential adverse effects on the breastfed child from Herceptin or from the underlying maternal condition
  • Encourage women who receive Herceptin during pregnancy or within 7 months prior to conception to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 or visiting http://www.motherpregnancyregistry.com/
  • If Herceptin is administered during pregnancy, or if a patient becomes pregnant while receiving Herceptin or within 7 months following the last dose of Herceptin, health care providers and patients should immediately report Herceptin exposure to Genentech at 1-888-835-2555

Pulmonary Toxicity

  • Herceptin administration can result in serious and fatal pulmonary toxicity, which includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions
  • Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity
  • Discontinue Herceptin in patients experiencing pulmonary toxicity

Exacerbation of Chemotherapy-Induced Neutropenia

  • In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received Herceptin and those who did not

Most Common Adverse Reactions

  • The most common adverse reactions associated with Herceptin use were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see additional select Important Safety Information throughout, and the accompanying full Prescribing Information, including Boxed WARNINGS.

Indication

PERJETA® (pertuzumab) is a HER2/neu receptor antagonist indicated for:

  • Treatment of metastatic breast cancer in combination with Herceptin® (trastuzumab) and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease
  • Use in combination with trastuzumab and docetaxel as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. This indication is based on demonstration of an improvement in pathological complete response rate. No data are available demonstrating improvement in event-free survival or overall survival

Limitations of Use:

  • The safety of PERJETA as part of a doxorubicin-containing regimen has not been established
  • The safety of PERJETA administered for greater than 6 cycles for early breast cancer has not been established

Important Safety Information

Boxed WARNINGS: Left Ventricular Dysfunction and Embryo-Fetal Toxicity

  • PERJETA administration can result in subclinical and clinical cardiac failure manifesting as decreased LVEF and CHF. Evaluate cardiac function prior to and during treatment. Discontinue PERJETA treatment for a confirmed clinically significant decrease in left ventricular function
  • Exposure to PERJETA can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception
    • Based on its mechanism of action and findings in animal studies, PERJETA can cause fetal harm when administered to a pregnant woman. PERJETA is a HER2/neu receptor antagonist. Cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported with use of another HER2/neu receptor antagonist (trastuzumab) during pregnancy. In an animal reproduction study, administration of pertuzumab to pregnant cynomolgus monkeys during the period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal death at exposures 2.5 to 20 times the exposure in humans at the recommended dose, based on Cmax
    • Verify the pregnancy status of females of reproductive potential prior to the initiation of PERJETA. Advise pregnant women and females of reproductive potential that exposure to PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm, including embryo-fetal death or birth defects. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of PERJETA in combination with trastuzumab
    • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PERJETA during pregnancy. Encourage women who receive PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception, to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 or visiting http://www.motherpregnancyregistry.com/
    • If PERJETA is administered during pregnancy, or if a patient becomes pregnant while receiving PERJETA or within 7 months following the last dose of PERJETA in combination with trastuzumab, health care providers and patients should immediately report PERJETA exposure to Genentech at 1-888-835-2555

Additional Important Safety Information

PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients.

Left Ventricular Dysfunction (LVD)

  • In Study 1, for patients with MBC, PERJETA in combination with Herceptin and docetaxel was not associated with increases in the incidence of symptomatic left ventricular systolic dysfunction (LVSD) or decreases in left ventricular ejection fraction (LVEF) compared with placebo in combination with Herceptin and docetaxel. Left ventricular dysfunction occurred in 4.4% of patients in the PERJETA-treated group and in 8.3% of patients in the placebo-treated group. Symptomatic LVSD (congestive heart failure) occurred in 1.0% of patients in the PERJETA-treated group and in 1.8% of patients in the placebo-treated group
  • Patients who have received prior anthracyclines or prior radiotherapy to the chest area may be at higher risk of decreased LVEF
  • In Study 2, for patients treated in the neoadjuvant setting, the incidence of LVSD was higher in the PERJETA-treated groups compared to the trastuzumab and docetaxel–treated group. An increased incidence of LVEF declines was observed in patients treated with PERJETA in combination with trastuzumab and docetaxel. In the overall treatment period, LVEF decline >10% and a drop to less than 50% occurred in 1.9% of patients treated with neoadjuvant trastuzumab and docetaxel as compared to 8.4% of patients treated with neoadjuvant PERJETA in combination with trastuzumab and docetaxel. Symptomatic LVSD occurred in 0.9% of patients treated with neoadjuvant PERJETA in combination with trastuzumab and in no patients in the other 3 arms. LVEF recovered to ≥50% in all patients
  • In Study 3, for patients treated in the neoadjuvant setting, in the overall treatment period, LVEF decline ˃10% and a drop to less than 50% occurred in 6.9% of patients treated with PERJETA plus trastuzumab and FEC followed by PERJETA plus trastuzumab and docetaxel, in 16.0% of patients treated with PERJETA plus trastuzumab and docetaxel following FEC, and in 10.5% of patients treated with PERJETA in combination with TCH. Symptomatic LVSD occurred in 4.0% of patients treated with PERJETA plus trastuzumab and docetaxel following FEC, in 1.3% of patients treated with PERJETA in combination with TCH, and in none of the patients treated with PERJETA plus trastuzumab and FEC followed by PERJETA plus trastuzumab and docetaxel. LVEF recovered to ≥50% in all but one patient
  • Assess LVEF prior to initiation of PERJETA and at regular intervals (eg, every 3 months in the metastatic setting and every 6 weeks in the neoadjuvant setting) during treatment to ensure that LVEF is within your institution’s normal limits
  • If LVEF is <45%, or is 45% to 49% with a 10% or greater absolute decrease below the pretreatment value, withhold PERJETA and Herceptin and repeat LVEF assessment within approximately 3 weeks. Discontinue PERJETA and Herceptin if the LVEF has not improved or has declined further, unless benefits for the individual patient outweigh the risks

Infusion-Related Reactions

  • PERJETA has been associated with infusion reactions
  • In Study 1, on the first day, when only PERJETA was administered, the overall frequency of infusion reactions was 13.0% in the PERJETA-treated group and 9.8% in the placebo-treated group, with the majority being mild to moderate. The most common infusion reactions (≥1.0%) were pyrexia, chills, fatigue, headache, asthenia, hypersensitivity, and vomiting. During the second cycle, when all drugs were administered on the same day, the most common infusion reactions in the PERJETA-treated group (≥1.0%) were fatigue, dysgeusia, hypersensitivity, myalgia, and vomiting
  • In Study 2 and Study 3, PERJETA was administered on the same day as the other study treatment drugs. Infusion reactions were consistent with those observed in Study 1, with a majority of reactions being National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v3.0) Grades 1-2
  • Observe patients closely for 60 minutes after the first infusion and for 30 minutes after subsequent infusions of PERJETA. If a significant infusion reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies. Monitor patients carefully until complete resolution of signs and symptoms. Consider permanent discontinuation in patients with severe infusion reactions

Hypersensitivity Reactions/Anaphylaxis

  • In Study 1, the overall frequency of hypersensitivity/anaphylaxis reactions was 10.8% in the PERJETA-treated group and 9.1% in the placebo-treated group. The incidence of Grades 3-4 hypersensitivity/anaphylaxis reactions was 2.0% in the PERJETA-treated group and 2.5% in the placebo-treated group according to NCI-CTCAE (version 3). Overall, 4 patients in the PERJETA-treated group and 2 patients in the placebo-treated group experienced anaphylaxis
  • In Study 2 and Study 3, hypersensitivity/anaphylaxis events were consistent with those observed in Study 1. In Study 2, two patients in the PERJETA and docetaxel-treated group experienced anaphylaxis. In Study 3, the overall frequency of hypersensitivity/anaphylaxis was highest in the PERJETA plus TCH-treated group (13.2%), of which 2.6% were NCI-CTCAE (version 3) Grades 3-4
  • Patients should be observed closely for hypersensitivity reactions. Severe hypersensitivity, including anaphylaxis, has been observed in clinical trials with treatment of PERJETA. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients

HER2 Testing

  • Detection of HER2 protein overexpression is necessary for selection of patients appropriate for PERJETA therapy because these are the only patients studied and for whom benefit has been shown. Patients with breast cancer were required to have evidence of HER2 overexpression defined as 3+ IHC or FISH amplification ratio ≥2.0 in the clinical studies. Only limited data were available for patients whose breast cancer was positive by FISH, but did not demonstrate protein overexpression by IHC
  • Assessment of HER2 status should be performed by laboratories using FDA-approved tests with demonstrated proficiency in the specific technology being utilized

Most Common Adverse Reactions

Metastatic Breast Cancer

  • The most common adverse reactions (>30%) seen with PERJETA in combination with Herceptin and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy. The most common NCI-CTCAE (version 3) Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, leukopenia, diarrhea, peripheral neuropathy, anemia, asthenia, and fatigue

Neoadjuvant Treatment of Breast Cancer

  • The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel were alopecia, diarrhea, nausea, and neutropenia. The most common NCI-CTCAE v3.0 Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, leukopenia, and diarrhea
  • The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel when given for 3 cycles following 3 cycles of FEC were fatigue, alopecia, diarrhea, nausea, vomiting, and neutropenia. The most common NCI-CTCAE (version 3) Grades 3-4 adverse reactions (>2%) were neutropenia, leukopenia, febrile neutropenia, diarrhea, left ventricular dysfunction, anemia, dyspnea, nausea, and vomiting
  • The most common adverse reactions (>30%) with PERJETA in combination with docetaxel, carboplatin, and trastuzumab (TCH) for 6 cycles were fatigue, alopecia, diarrhea, nausea, vomiting, neutropenia, thrombocytopenia, and anemia. The most common NCI-CTCAE (version 3) Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, anemia, leukopenia, diarrhea, thrombocytopenia, vomiting, fatigue, ALT increased, hypokalemia, and hypersensitivity

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see additional select Important Safety Information throughout, and the accompanying full Prescribing Information including Boxed WARNINGS.

Indication

KADCYLA® (ado-trastuzumab emtansine), as a single agent, is indicated for the treatment of patients with HER2-positive (HER2+), metastatic breast cancer (MBC) 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

Important Safety Information

Warnings and Precautions

Hepatotoxicity (Boxed WARNING)

Hepatotoxicity, predominantly in the form of asymptomatic increases in the concentrations of serum transaminases, has been observed in clinical trials with KADCYLA.

Serious hepatobiliary disorders, including at least 2 fatal cases of severe drug-induced liver injury and associated hepatic encephalopathy, have been reported in clinical trials with KADCYLA. Some of the observed cases may have been confounded by comorbidities and concomitant medications with known hepatotoxic potential.

Monitor serum transaminases and bilirubin prior to initiation of KADCYLA treatment and prior to each KADCYLA dose. Patients with known active hepatitis B virus or hepatitis C virus were excluded from EMILIA. Reduce dose or discontinue KADCYLA as appropriate in cases of increased serum transaminases and/or total bilirubin. Permanently discontinue KADCYLA treatment in patients with serum transaminases >3×ULN and concomitant total bilirubin >2×ULN.

In clinical trials of KADCYLA, cases of nodular regenerative hyperplasia (NRH) of the liver have been identified from liver biopsies (3 cases out of 884 treated patients, 1 of which was fatal). NRH should be considered in all patients with clinical symptoms of portal hypertension and/or cirrhosis-like pattern seen on the computed tomography scan of the liver but with normal transaminases and no manifestations of cirrhosis. Diagnosis can be confirmed only by histopathology. Upon diagnosis, KADCYLA treatment must be permanently discontinued.

Left Ventricular Dysfunction (Boxed WARNING)

Patients treated with KADCYLA are at increased risk of developing left ventricular dysfunction (LVD). A decrease of left ventricular ejection fraction (LVEF) to <40% has been observed in patients treated with KADCYLA. In EMILIA, left ventricular dysfunction occurred in 1.8% of patients in the KADCYLA-treated group and 3.3% of patients in the comparator group.

Assess LVEF prior to initiation of KADCYLA and at regular intervals (eg, every 3 months) during treatment. Treatment with KADCYLA has not been studied in patients with LVEF <50% prior to treatment. If, at routine monitoring, LVEF is <40%, or is 40% to 45% with a 10% or greater absolute decrease below the pretreatment value, withhold KADCYLA and repeat LVEF assessment within approximately 3 weeks. Permanently discontinue KADCYLA if the LVEF has not improved or has declined further.

Embryo-Fetal Toxicity (Boxed WARNING)

KADCYLA can cause fetal harm when administered to a pregnant woman. Treatment with trastuzumab, the antibody component of KADCYLA, during pregnancy in the postmarketing setting has resulted in cases of oligohydramnios; oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death were observed in the postmarketing setting in patients treated with trastuzumab. DM1, the cytotoxic component of KADCYLA, can cause embryo-fetal toxicity, based on its mechanism of action.

Verify the pregnancy status of women of reproductive potential prior to the initiation of KADCYLA. Advise pregnant women and females of reproductive potential that exposure to KADCYLA during pregnancy or within 7 months prior to conception can result in fetal harm. Advise women of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of KADCYLA.

If KADCYLA is administered during pregnancy or if a patient becomes pregnant while receiving KADCYLA or within 7 months following the last dose of KADCYLA, immediately report exposure to the Genentech Adverse Event Line at 1-888-835-2555.

Encourage women who may be exposed to KADCYLA during pregnancy or within 7 months prior to conception, to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 or visiting http://www.motherpregnancyregistry.com/.

Pulmonary Toxicity

Cases of interstitial lung disease (ILD), including pneumonitis, some leading to acute respiratory distress syndrome or fatal outcome, have been reported in clinical trials with KADCYLA. Signs and symptoms include dyspnea, cough, fatigue, and pulmonary infiltrates. In EMILIA, the overall frequency of pneumonitis was 1.2%.

Treatment with KADCYLA should be permanently discontinued in patients diagnosed with ILD or pneumonitis.

Patients with dyspnea at rest due to complications of advanced malignancy and comorbidities may be at increased risk of pulmonary events.

Infusion-Related Reactions, Hypersensitivity Reactions

Treatment with KADCYLA has not been studied in patients who had trastuzumab permanently discontinued due to infusion-related reactions (IRR) and/or hypersensitivity; treatment with KADCYLA is not recommended for these patients.

Infusion-related reactions characterized by one or more of the following symptoms—flushing, chills, pyrexia, dyspnea, hypotension, wheezing, bronchospasm, and tachycardia—have been reported in clinical trials of KADCYLA. In the randomized trial, the overall frequency of IRRs in patients treated with KADCYLA was 1.4%. In most patients, these reactions resolved over the course of several hours to a day after the infusion was terminated.

KADCYLA treatment should be interrupted in patients with severe IRRs and permanently discontinued in the event of a life-threatening IRR. Patients should be observed closely for IRRs, especially during the first infusion.

One case of a serious, allergic/anaphylactoid-like infusion reaction has been observed in clinical trials of single-agent KADCYLA. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use.

Hemorrhage

Cases of hemorrhagic events, including central nervous system, respiratory, and gastrointestinal hemorrhage, have been reported in clinical trials with KADCYLA. Some of these bleeding events resulted in fatal outcomes. In EMILIA the incidence of ≥Grade 3 hemorrhage was 1.8% in the KADCYLA-treated group and 0.8% in the comparator group.

Although in some of the observed cases the patients were also receiving anticoagulation therapy or antiplatelet therapy, or had thrombocytopenia, in others there were no known additional risk factors. Anticoagulation therapy and antiplatelet agents may increase the risk of bleeding. Use caution with these agents and consider additional monitoring when concomitant use is medically necessary.

Thrombocytopenia

Thrombocytopenia was reported in clinical trials of KADCYLA. The majority of these patients had Grade 1 or 2 events (<LLN to ≥50,000/mm3), with the nadir occurring by day 8 and generally improving to Grade 0 or 1 (≥75,000/mm3) by the next scheduled dose. In clinical trials of KADCYLA, the incidence and severity of thrombocytopenia were higher in Asian patients.

In EMILIA, the incidence of ≥Grade 3 thrombocytopenia was 14.5% in the KADCYLA-treated group and 0.4% in the comparator group. In Asian patients, the incidence of ≥Grade 3 thrombocytopenia was 45.1% in the KADCYLA group and 1.3% in the comparator group.

Monitor platelet counts prior to initiation of KADCYLA and prior to each KADCYLA dose. KADCYLA has not been studied in patients with platelet counts ≤100,000/mm3 prior to initiation of treatment. In the event of decreased platelet count to Grade 3 or greater (<50,000/mm3), do not administer KADCYLA until platelet counts recover to Grade 1 (≥75,000/mm3). Patients with thrombocytopenia (≤100,000/mm3) prior to initiation of KADCYLA and patients on anticoagulant treatment should be closely monitored during treatment with KADCYLA.

Neurotoxicity

Peripheral neuropathy, mainly as Grade 1 and predominantly sensory, was reported in clinical trials of KADCYLA. In EMILIA, the incidence of ≥Grade 3 peripheral neuropathy was 2.2% in the KADCYLA-treated group and 0.2% in the comparator group.

KADCYLA should be temporarily discontinued in patients experiencing Grade 3 or 4 peripheral neuropathy until resolution to ≤Grade 2. Patients should be clinically monitored on an ongoing basis for signs/symptoms of neurotoxicity.

HER2 Testing

Detection of HER2 protein overexpression or gene amplification is necessary for selection of patients appropriate for KADCYLA therapy, because these are the only patients studied for whom benefit has been shown. Assessment of HER2 status should be done using an FDA-approved test performed by laboratories with demonstrated proficiency.

In the randomized study, patients with breast cancer were required to have evidence of HER2 overexpression defined as 3+ IHC and/or FISH amplification ratio ≥2.0 assessed by a validated test.

Extravasation

In KADCYLA clinical studies, reactions secondary to extravasation have been observed. These reactions, observed more frequently within 24 hours of infusion, were usually mild and comprised erythema, tenderness, skin irritation, pain, or swelling at the infusion site. The infusion site should be closely monitored for possible subcutaneous infiltration during drug administration. Specific treatment for KADCYLA extravasation is unknown.

Use in Specific Populations

Nursing Mothers

There is no information regarding the presence of ado-trastuzumab emtansine in human milk, the effects on the breastfed infant, or the effects on milk production. DM1, the cytotoxic component of KADCYLA, may cause serious adverse reactions in breastfed infants, based on its mechanism of action. Advise women not to breastfeed during treatment and for 7 months following the last dose of KADCYLA.

You are encouraged to report side effects to Genentech and the FDA. You may contact Genentech by calling 1-888-835-2555. You may contact the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.

Please see accompanying full Prescribing Information for additional Important Safety Information, including Boxed WARNINGS.