Pertuzumab

May result in cardiac failure (clinical and subclinical) manifesting as decreased left ventricular ejection fraction (LVEF) and heart failure (HF). Assess cardiac function at baseline and at regular intervals during treatment. Discontinue for confirmed clinically significant decline in left ventricular function. Decreases in LVEF are associated with HER2 inhibitors, including pertuzumab. Patients who received prior anthracycline therapy or chest irradiation may be at an increased risk for cardiotoxicity. In studies of pertuzumab (versus placebo) in combination with trastuzumab and docetaxel for the treatment of metastatic breast cancer, the rate of cardiotoxicity (LVEF decline or symptomatic LV systolic dysfunction) was not increased in the pertuzumab group when compared to placebo. In the early breast cancer neoadjuvant setting, the incidence of LV dysfunction was higher in patients treated with pertuzumab. In the early breast cancer adjuvant setting, the incidence of symptomatic heart failure was slightly higher in patients treated with pertuzumab (most of these events were reported in anthracycline-treated patients); approximately half of the pertuzumab-treated patients who experienced symptomatic heart failure recovered. Of note, patients with pretreatment LVEF ≤50%, CHF, LVEF decreases to 360 mg/m2 doxorubicin or its equivalent) were excluded from studies. Assess LVEF at baseline and approximately every 12 weeks during treatment. Withhold pertuzumab and trastuzumab for a

Diarrhea occurred more frequently in patients receiving pertuzumab in combination with trastuzumab and docetaxel, compared to patients receiving only trastuzumab and docetaxel.

Infusion reactions (either during or on the day of infusion) have been associated with pertuzumab; commonly described as fever, chills, fatigue, headache, weakness, myalgia, hypersensitivity, abnormal taste or vomiting. Grade 3 or 4 infusion reactions occurred rarely. The incidence of hypersensitivity/anaphylaxis was slightly higher in the group receiving pertuzumab (compared to placebo) in combination with trastuzumab and docetaxel. Monitor for 1 hour after the first infusion and for 30 minutes after subsequent infusions. For significant infusion reactions, interrupt or slow infusion rate; for severe infusion reactions, consider permanently discontinuing. Medications and equipment for the treatment of hypersensitivity should be available for immediate use during infusion. Concomitant drug therapy issues:

For pertuzumab, trastuzumab, and taxane combination regimens, pertuzumab and trastuzumab may be administered in any order; however, the taxane should be given after pertuzumab and trastuzumab. Pertuzumab and trastuzumab should be administered following completion of the anthracycline therapy in patients receiving anthracycline-based regimens.

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Pertuzumab exposure during pregnancy may result in embryo-fetal mortality and birth defects. Advise patients of the risks and the need for effective contraception. Verify pregnancy status prior to treatment initiation. Effective contraception should be used by all patients receiving pertuzumab during therapy and for 7 months after the last dose (of pertuzumab in combination with trastuzumab) for women of childbearing potential. Other warnings/precautions:

Establish HER2 status prior to treatment. Improper assay performance (including suboptimally fixed tissue, failure to use specified reagents, deviation from assay instructions, and failure to include appropriate assay controls) may lead to unreliable results. Information on tests is available at http://www.fda.gov/CompanionDiagnostics.