IMPORTANT SAFETY INFORMATION

Cardiomyopathy

• OGIVRI administration can result in sub-clinical and clinical cardiac failure. The incidence and severity are highest in patients receiving OGIVRI with anthracycline-containing chemotherapy regimens
• OGIVRI can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. OGIVRI can also cause asymptomatic decline in left ventricular ejection fraction (LVEF). Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan
• Evaluate left ventricular function in all patients prior to and during treatment with OGIVRI
• Discontinue OGIVRI treatment in patients receiving adjuvant therapy and withhold OGIVRI in patients with metastatic disease for clinically significant decrease in left ventricular function

Infusion Reactions

• OGIVRI administration can result in serious and fatal infusion reactions
• Symptoms usually occur during or within 24 hours of OGIVRI administration
• Interrupt OGIVRI infusion for dyspnea or clinically significant hypotension
• Monitor patients until symptoms completely resolve
• Discontinue OGIVRI 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 OGIVRI 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 OGIVRI
• Advise pregnant women and females of reproductive potential that exposure to OGIVRI 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 OGIVRI. Advise female patients to contact their healthcare provider with a known or suspected pregnancy
• Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for OGIVRI treatment and any potential adverse effects on the breastfed child from OGIVRI or from the underlying maternal condition

Pulmonary Toxicity

• OGIVRI 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 OGIVRI 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 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

Most Common Adverse Reactions

• Adjuvant Breast Cancer: Most common adverse reactions (≥ 5%) are headache, diarrhea, nausea, and chills.
• Metastatic Breast Cancer: Most common adverse reactions (≥ 10%) are fever, chills, headache, infection, congestive heart failure, insomnia, cough, and rash.
• Metastatic Gastric Cancer: Most common adverse reactions (≥ 10%) are neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia.

INDICATIONS

Adjuvant Breast Cancer

OGIVRI 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 OGIVRI.

^* 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

OGIVRI 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 OGIVRI.

Metastatic Gastric Cancer

OGIVRI 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 OGIVRI.