PERJETA Rx

Indication(s):

In combination with trastuzumab and docetaxel: to treat patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Pharmacology:

Pertuzumab targets the extracellular dimerization domain of the HER2 protein and, thereby, blocks ligand-dependent heterodimerization of HER2 with others, including EGFR, HER3 and HER4. As a result, pertuzumab inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated protein kinase and phosphoinositide 3-kinase. Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. In addition, pertuzumab mediates antibody-dependent cell-mediated cytotoxicity.

Clinical Trials:

Perjeta was assessed in a randomized trial of 808 patients with HER2-positive metastatic breast cancer. Breast tumor specimens were required to show HER2 overexpression. Patients were randomized 1:1 to receive placebo + trastuzumab and docetaxel or Perjeta + trastuzumab and docetaxel. Perjeta was given by IV at an initial dose of 840mg, followed by 420mg every 3 weeks thereafter. Trastuzumab was given by IV at an initial dose of 8mg/kg, followed by 6mg/kg every 3 weeks thereafter. Patients were treated with Perjeta and trastuzumab until progression of disease, withdrawal of consent, or unacceptable toxicity. Docetaxel was given as an initial dose of 75mg/m2 by IV infusion every 3 weeks for at least 6 cycles. The docetaxel dose could be escalated to 100mg/m2 at the investigator’s discretion if the initial dose was well tolerated.

The primary endpoint of the randomized trial was progression-free survival (PFS) as assessed by an independent review facility (IRF). PFS was defined as the time from the date of randomization to the date of disease progression or death (from any cause) if the death occurred within 18 weeks of the last tumor assessment. Additional endpoints included overall survival (OS), PFS (investigator-assessed), objective response rate (ORR) and duration of response.

The randomized trial demonstrated a statistically significant improvement in IRF-assessed PFS in the Perjeta-treated group compared with the placebo-treated group [hazard ratio (HR) = 0.62 (95% CI: 0.51, 0.75), P< 0.0001] and an increase in median PFS of 6.1 months (median PFS of 18.5 months in the Perjeta group vs. 12.4 months in the placebo group). The results for investigator-assessed PFS were comparable to those observed for IRF-assessed PFS.

Legal Classification:

Rx

Adults:

In combination with trastuzumab and docetaxel: initially 840mg IV over 60 minutes, followed every 3 weeks thereafter by a dose of 420mg IV over 30–60 minutes. Dose modification (missed dose, LVEF, or infusion reactions): see literature.

Children:

Not established.

Warnings/Precautions:

Risk of embryo-fetal toxicity. Pretreatment LVEF value of ≤50%, history of CHF, decreases in LVEF to <50% during prior trastuzumab therapy, uncontrolled hypertension, recent MI, serious cardiac arrythmia requiring treatment or a cumulative prior anthracycline exposure to >360mg/m2 of doxorubicin or its equivalent: not studied. Assess LVEF at baseline and every 3 months during treatment; if LVEF is <40%, or is 40% to 45% with a ≥10% absolute decrease below the pretreatment value, withhold and repeat LVEF within 3 weeks; discontinue if LVEF has not improved. Monitor for signs/symptoms of infusion reactions; slow or interrupt infusion and treat if occurs; discontinue if severe. Test for HER2 protein overexpression using FDA-approved tests by labs with demonstrated proficiency. Pregnancy (Cat.D); use adequate contraception during and at least 6 months after therapy. Nursing mothers: not recommended.

Adverse Reaction(s)

Diarrhea, alopecia, neutropenia, nausea, fatigue, rash, peripheral neuropathy; decreases in LVEF; pregnant women: possible oligohydramnios (monitor).

How Supplied:

Single-use vial—1

LAST UPDATED:

10/31/2012