Herceptin^®

trastuzumab

Indications & Important Safety Information

Herceptin: Indications

Adjuvant Breast Cancer

Herceptin 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

Metastatic Gastric Cancer

Herceptin is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.

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

Herceptin HYLECTA: Indications

Adjuvant Breast Cancer

HERCEPTIN HYLECTA (trastuzumab and hyaluronidase-oysk) is indicated for adjuvant treatment of adults with 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 trastuzumab
*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 HYLECTA is indicated in adults:

• 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 trastuzumab

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 breast cancer 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
• 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 in breast cancer were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia
• The most common adverse reactions associated with Herceptin in metastatic gastric cancer were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia

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.
 

Herceptin HYLECTA: BOXED WARNINGS and Additional Important Safety Information
Cardiomyopathy

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

Pulmonary Toxicity

• HERCEPTIN HYLECTA administration can result in serious and fatal pulmonary toxicity. Symptoms usually occur during or within 24 hours of HERCEPTIN HYLECTA administration. Discontinue HERCEPTIN HYLECTA for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Monitor patients until symptoms completely resolve

Embryo-Fetal Toxicity

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

Cardiac Monitoring

• Evaluate cardiac function prior to and during treatment
• 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 HYLECTA treatment
• Monitor more frequently if HERCEPTIN HYLECTA is withheld for significant left ventricular cardiac dysfunction

Embryo-Fetal Toxicity

• Exposure to HERCEPTIN HYLECTA 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 HYLECTA
• Advise pregnant women and females of reproductive potential that exposure to HERCEPTIN HYLECTA 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 HYLECTA
• Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for HERCEPTIN HYLECTA treatment and any potential adverse effects on the breastfed child from HERCEPTIN HYLECTA or from the underlying maternal condition
• If HERCEPTIN HYLECTA is administered during pregnancy, or if a patient becomes pregnant while receiving HERCEPTIN HYLECTA or within 7 months following the last dose of HERCEPTIN HYLECTA, health care providers and patients should immediately report HERCEPTIN HYLECTA exposure to Genentech at 1-888-835-2555

Pulmonary Toxicity

• HERCEPTIN HYLECTA 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.
• 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 HYLECTA in patients experiencing pulmonary toxicity

Exacerbation of Chemotherapy-Induced Neutropenia

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

Hypersensitivity and Administration-Related Reactions

• Severe administration-related reactions (ARRs), including hypersensitivity and anaphylaxis, have been reported with HERCEPTIN HYLECTA. Patients experiencing dyspnea at rest due to complications of advanced malignancy and comorbidities may be at increased risk of a severe or of a fatal ARR.
• In the HannaH and SafeHER trials, 9% and 4.2% of patients experienced Grade 1-4 hypersensitivity and anaphylaxis, respectively. Grade 3-4 hypersensitivity and anaphylactic reactions occurred in 1% and <1% of the patients treated with HERCEPTIN HYLECTA, respectively. In the SafeHER trial, 2 patients required permanent treatment discontinuation with HERCEPTIN HYLECTA; 1 patient due to a hypersensitivity reaction and 1 patient due to anaphylaxis. Serious and fatal reactions have been reported after treatment with intravenous trastuzumab products
• Closely monitor patients for systemic hypersensitivity reactions, especially during the first administration. Permanently discontinue HERCEPTIN HYLECTA in patients who experience anaphylaxis or severe hypersensitivity reactions. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. For patients experiencing reversible Grade 1 or 2 hypersensitivity reactions, consider pre-medication with an analgesic, antipyretic, or an antihistamine prior to re-administration of HERCEPTIN HYLECTA

Most Common Adverse Reactions
Adjuvant Breast Cancer

• Most common adverse reactions for HERCEPTIN HYLECTA are fatigue, arthralgia, diarrhea, injection site reaction, upper respiratory tract infection, rash, myalgia, nausea, headache, edema, flushing, pyrexia, cough, and pain in extremity.

Metastatic Breast Cancer (based on intravenous trastuzumab)

• Most common adverse reactions are fever, chills, headache, infection, congestive heart failure, insomnia, cough, and rash.

You may report side effects to the FDA at 800–FDA–1088 or http://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.