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Pertuzumab (Perjeta) Regimen Extends Survival in Women With Metastatic Breast Cancer

Treatment compared with trastuzumab and chemotherapy in phase III study

Positive results have been reported from the phase III Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) trial, which showed that adding pertuzumab (Perjeta, Genentech) to trastuzumab (Herceptin, Genentech) and docetaxel chemotherapy extended the lives (overall survival [OS]) of patients with previously untreated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) by 15.7 months compared with trastuzumab and chemotherapy (median OS: 56.5 vs. 40.8 months, respectively).

The new data were presented September 28 at the European Society for Medical Oncology (ESMO) 2014 congress in Madrid, Spain.

Pertuzumab in combination with trastuzumab and docetaxel chemotherapy is approved in the U.S. for the treatment of patients with previously untreated HER2-positive MBC.

The CLEOPATRA trial was an international, randomized, double-blind, placebo-controlled study comparing the combination of pertuzumab, trastuzumab, and docetaxel chemotherapy with placebo, trastuzumab, and chemotherapy in 808 patients with previously untreated HER2-positive MBC, or with HER2-positive MBC that had returned after prior therapy in the adjuvant or neoadjuvant setting. The study’s primary endpoint was progression-free survival (PFS). Secondary endpoints included OS and the treatment’s safety profile.

An interim analysis of OS from the CLEOPATRA study was presented in 2012 at the San Antonio Breast Cancer Symposium. At that time, median OS had not yet been reached for patients receiving the pertuzumab regimen, as more than half of the patients continued to survive.

The new results are from the final pre-specified OS analysis after a median follow-up period of 50 months; median OS has now been reached for patients receiving the pertuzumab regimen.

Updates to previously reported OS, PFS, and safety-profile data from the CLEOPATRA study showed the following:

  • The risk of death was reduced by 32% in patients treated with the pertuzumab regimen compared with those who received trastuzumab and chemotherapy (hazard ratio [HR] = 0.68; P = 0.0002).
  • Patients who received the pertuzumab regimen experienced a 32% reduction in PFS (HR = 0.68) compared with those who received trastuzumab and chemotherapy.
  • With longer follow-up, the median improvement in PFS of more than 6 months was maintained (median PFS: 18.7 months for patients treated with pertuzumab, trastuzumab, and chemotherapy compared with 12.4 months for those who received trastuzumab and chemotherapy).
  • The most common adverse events with the pertuzumab regimen included hair loss, diarrhea, low white blood cell (WBC) count, rash, mucosal inflammation, headache, upper respiratory tract infection, itching, dry skin, muscle spasms, and low WBC count with fever.

Pertuzumab targets HER2, a protein found on the surfaces of many normal cells and in high quantities on the surfaces of cancer cells in HER2-positive cancers. Pertuzumab is designed to prevent HER2 from pairing (dimerizing) with other HER receptors (EGFR/HER1, HER3, and HER4) on the surface of cells, 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 HER2, but at different places on the receptor. The combination of pertuzumab and trastuzumab is thought to provide a more comprehensive blockade of HER signaling pathways.

Source: Genentech; September 28, 2014.

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