Pertuzumab

Pertuzumab is used for: Metastatic Breast Cancer, Neoadjuvant Treatment of Breast Cancer

Metastatic Breast Cancer Indicated in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer in patients who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease Initial dose: 840 mg IV infusion over 60 min, THEN 420 mg IV infusion over 30-60 min q3wk Trastuzumab: 8 mg/kg IV infusion over 90 min initially, then 6 mg/kg IV infusion over 30-90 min q3wk Docetaxel: 75 mg/m² IV infusion initially; may increase to 100 mg/m² IV infusion q3wk if initial dose is well tolerated Neoadjuvant Treatment of Breast Cancer Indicated in combination with trastuzumab and docetaxel for the 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 Initial dose: 840 mg IV infusion over 60 min, THEN 420 mg IV infusion over 30-60 min q3wk Trastuzumab: 8 mg/kg IV infusion over 90 min initially, then 6 mg/kg IV infusion over 30-90 min q3wk Docetaxel: 75 mg/m² IV infusion initially; may increase to 100 mg/m² IV infusion q3wk if initial dose is well tolerated Neoadjuvant dosage regimens Administered q3wk for 3 to 6 cycles as part of 1 of the following treatment regimens for early breast cancer: - 4 preoperative cycles of pertuzumab in combination with trastuzumab and docetaxel followed by 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) -3 preoperative cycles of FEC alone followed by 3 preoperative cycles of pertuzumab in combination with docetaxel and trastuzumab -6 preoperative cycles of pertuzumab in combination with docetaxel, carboplatin, and trastuzumab (TCH) (escalation of docetaxel above 75 mg/m2 is not recommended) Following surgery, patients should continue to receive trastuzumab to complete 1 year of treatment

IV Preparation Withdraw appropriate volume for desired dose from vial(s) Dilute measured dose into 0.9% NaCl 250 ml infusion bag (dilute with 0.9% NaCl only, do not use dextrose solution) Do not shake; mix diluted solution by gentle inversion Administer immediately once prepared or store refrigerated IV Administration Administer initial dose as IV infusion over 60 minutes; subsequent doses may be administered over 30-60 minutes Interrupt or decrease infusion rate if infusion-associated reaction occurs Administer by IV infusion only; do not give IV push

Hypersensitivity

Risk of left ventricular dysfunction (including CHF), infusion-related reactions & febrile neutropenia. Assess LVEF prior to initiation & every 3 cycles (in the metastatic setting) & every 6 wk (in the neoadjuvant setting) during treatment. Close observation during & for 60 min after the 1st infusion & during & for 30-60 min after subsequent infusions. Not recommended in pregnancy & in women of childbearing potential not using contraception. Lactation. Childn & adolescents 48 yr. Verify pregnancy status of females of reproductive potential prior to the initiation of therapy; advise pregnant women and females of reproductive potential that therapy during pregnancy or within 7 months prior to conception can result in fetal harm. Lactation: Unknown whether distributed in breast milk; because of potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue breast feeding or discontinue the drug, taking into account the importance of the drug to the mother.

Pregnancy Based on its mechanism of action and findings in animal studies, therapy can cause fetal harm when administered to a pregnant woman; there are no available data on use of drug in pregnant women; however, in post-marketing reports, use of another HER2/neu receptor antagonist (trastuzumab) during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death Monitor women who received drug in combination with trastuzumab during pregnancy or within 7 months prior to conception for oligohydramnios; if oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care Verify pregnancy status of females of reproductive potential prior to initiation of therapy Based on mechanism of action and animal data, drug can cause embryo-fetal harm when administered during pregnancy; advise females of reproductive potential to use effective contraception during treatment and for 7 months following last dose in combination with trastuzumab Animal data In an animal reproduction study, administration to pregnant cynomolgus monkeys during period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal deaths at clinically relevant exposures that were 2.5 to 20-fold greater than exposures in humans receiving the recommended dose, based on Cmax; apprise patient of potential risks to a fetus; there are clinical considerations if drug in combination with trastuzumab is used during pregnancy or within 7 months prior to conception Lactation There is no information regarding presence of drug in human milk, effects on breastfed infant or on milk production; published data suggest that human IgG is present in human milk but does not enter neonatal and infant circulation in substantial amounts; consider developmental and health benefits of breast feeding along with mother’s clinical need for treatment and any potential adverse effects on breastfed child or from underlying maternal condition; consideration should also take into account elimination half-life of pertuzumab and trastuzumab wash out period of 7 months

Side effects of Pertuzumab : >10% Diarrhea (66.8%) Alopecia (60.9%) Neutropenia (52.8%) Nausea (42.3%) Fatigue (37.6%) Rash (33.7%) Peripheral neuropathy (32.4%) Decreased appetite (29.2%) Mucosal inflammation (27.8%) Asthenia (26%) Vomiting (24.1%) Anemia (23.1%) Peripheral edema (23.1%) Nail disorder (22.9%) Myalgia (22.9%) Headache (20.9%) Stomatitis (18.9%) Pyrexia (18.7%) Dysgeusia (18.4%) Leukopenia (18.2%) Upper respiratory tract infection (16.7%) Arthralgia (15.5%) Constipation (15%) Pruritus (14%) Dyspnea (14%) Increased lacrimation (14%) Febrile neutropenia (13.8%) Insomnia (13.3%) Dizziness (12.5%) Nasopharyngitis (11.8%) Dry skin (10.6%) 1-10% Hypersensitivity (10%) Paronychia (7.1%) Pleural effusion (5.2%) Left ventricular dysfunction (4.4%) Congestive heart failure (1%)

Monoclonal antibody that binds to the extracellular dimerization domain of the human epidermal growth factor receptor 2 protein (HER2); mediates antibody-dependent cellular cytotoxicity by inhibiting proliferation of cells that overexpress HER2.