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Pertuzumab (Perjeta) Extends Survival in Patients With Metastatic Breast Cancer

Combo therapy reduces mortality risk by 34% (Dec. 8)

Updated survival results have been reported from the phase III CLEOPATRA study, which showed that the combination of pertuzumab (Perjeta, Roche), trastuzumab (Herceptin, Genentech), and docetaxel chemotherapy significantly extended the lives (overall survival) of patients with previously untreated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC), compared with trastuzumab, chemotherapy, and placebo.

The risk of death was reduced by 34% in patients who received pertuzumab, trastuzumab, and chemotherapy, compared with those who received trastuzumab and chemotherapy (hazard ratio [HR] = 0.66; P = 0.0008). At the time of the analysis, median overall survival had not been reached in patients receiving the pertuzumab-based combination, as more than half of these patients continued to survive. The median period of overall survival was more than 3 years (37.6 months) for patients who received trastuzumab and chemotherapy.

Pertuzumab targets the HER2 receptor — a protein found on the outside of cancer cells in HER2-positive cancers. Pertuzumab is believed to work in a way that is complementary to trastuzumab, as the two drugs target different locations on the HER2 receptor.

In June 2012, the FDA approved Perjeta (pertuzumab) in combination with trastuzumab and docetaxel chemotherapy for the treatment of patients with HER2-positive mBC who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

The new findings were reported at the 2012 CTRC–AACR San Antonio Breast Cancer Symposium.

The phase III, randomized, double-blind, placebo-controlled CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) trial evaluated the efficacy and safety profile of pertuzumab combined with trastuzumab and docetaxel chemotherapy compared with trastuzumab and docetaxel chemotherapy plus placebo in 808 patients with previously untreated HER2-positive mBC, or with HER2-positive mBC that had recurred after treatment in the adjuvant or neoadjuvant setting.

Pertuzumab prevents the HER2 receptor from pairing (dimerizing) with other HER receptors (EGFR/HER1, HER3, and HER4) on cell surfaces — a process that is believed to play a role in tumor growth and survival. The binding of pertuzumab to HER2 may also signal the body’s immune system to destroy the cancer cells. The mechanisms of action of pertuzumab and trastuzumab are believed to complement each other, as both bind to the HER2 receptor, but to different places. The combination of pertuzumab, trastuzumab, and docetaxel chemotherapy is thought to provide a more comprehensive blockade of HER signaling pathways.

Source: Roche; December 8, 2012.

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