What is the role of pertuzumab (Perjeta) in the treatment of HER2-positive breast cancer?

Updated: May 14, 2019
  • Author: Maurie Markman, MD, MS; Chief Editor: Karl S Roth, MD  more...
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Answer

Pertuzumab (Perjeta), a humanized monoclonal antibody that blocks the activation of the HER2 receptor by hindering dimerization, was approved by the FDA in combination with trastuzumab and docetaxel. This novel therapy is targeted at HER2- positive metastatic breast cancer patients previously not treated with hormone therapy or chemotherapy. Its future use in earlier stages is currently being investigated.

FDA-approval of pertuzumab was based on results from the Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) trial. Pertuzumab elicits action at a different ligand binding site from trastuzumab to prevent HER2 dimerization. The combination of both HER2 receptor antibodies (pertuzumab plus trastuzumab) is superior to either agent alone. The trial compared first-line trastuzumab plus docetaxel (plus placebo) to trastuzumab plus docetaxel plus pertuzumab in HER2-postive metastatic breast cancer. Results from the study showed an average increase in progression-free survival of 6.1 months in patients receiving pertuzumab in addition to trastuzumab and docetaxel with minimal to no increase in cardiac toxic effects. [16]

The FDA approved pertuzumab for neoadjuvant treatment in combination with trastuzumab and docetaxel for patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive). Approval was based on a randomized trial that compared a number of regimens with and without pertuzumab in women with HER2-positive breast cancer. In the trial, 39.3% of patients treated with pertuzumab, trastuzumab, and docetaxel (n = 107) achieved a pathologic complete response (pCR), compared with 21.5% of patients treated with trastuzumab and docetaxel (n = 107) at the time of surgery. [17]


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