Pertuzumab (Perjeta)

A monoclonal antibody that targets the extracellular dimerization domain of HER2 and inhibits the ligand no known dependent heterodimerization of HER2 with other HER2 family members.

For first line treatment of HER2 + metastatic breast cancer.

Approved for neoadjuvant treatment of breast cancer in combination with trastuzumab and docetaxel for patients with HER2 positive, locally advanced, inflammatory or early stage breast cancer and high-risk of recurrence, metastasis, or death.

Approval as an adjuvant treatment in combination with trastuzumab and chemotherapy in patients with HER2+ locally advanced, inflammatory, or early stage breast cancer.

A HER2/neu receptor antagonist indicated in combination with with trastuzumab and docetaxel for the treatment of HER2 positive metastic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic breast cancer.

Pertuzumab is a humanized monoclonal antibody that binds HER2 at different epitope of the HER2 extracellular domain than that trastuzumab binds.

Prevents HER2 from dimerizing with other ligand-activated HER receptors, most notably HER3.

Like trastuzumab it stimulates antibody-dependent cell mediated cytotoxicity.

The Clinical Evaluation of Pertuzumab and trastuzumab study (CLEOPATRA) assessed the efficacy and safety of these two agents plus docetaxel as compared with placebo plus trastuzumab plus docetaxel in first-line treatment for HER2 positive metastatic breast cancer:The combination when used as first-line treatment for HER 2 positive metastatic breast cancer, significantly prolonged progression free survival, with no increase in cardiac toxicity.

The addition of Pertuzumab to trastuzumab and docetaxel in the first line treatment of HER2 positive metastatic breast cancer achieved an absolute survival gain of 15.7 months versus trestrastuzumab and docetaxel alone.

In the phase II NeoSphere trial 417 patients with newly diagnosed HER-2 positive early stage breast cancer were randomized to one of for treatment arms: Trastuzumab plus docetaxel, pertuzamab plus trastuzumab plus docetaxel, pertuzumab plus trastuzumab or pertuzumab plus docetaxel-Patient’s had locally advanced for early breast cancer and were treated neo-adjuvantly-patient who received docetaxel, pertuzumab plus trastuzumab Had a significant improvement in pathological complete response of 45.8% impaired with 16.8-29% for the other groups.

Associated with embryo-fetal toxicity.

Associated with decreased left ventricular ejection occurs in 8.3% compared to 4,4% in a placebo group.

Left ventricular ejection fracture should be assessed prior to initiation of therapy, and should be rechecked every 3months.

Infusions associated with fatigue, dysguesia, hypersensitivity, myalgia, and vomiting.

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