What is the role of pertuzumab (Perjeta) in the adjuvant therapy for breast cancer?

Updated: May 21, 2019
  • Author: Erin V Newton, MD; Chief Editor: Neetu Radhakrishnan, MD  more...
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Pertuzumab (Perjeta), a humanized monoclonal antibody that blocks the activation of the HER2 receptor by hindering dimerization, was approved by the US Food and Drug Administration (FDA) in June 2012 in combination with trastuzumab and docetaxel for adjuvant treatment of metastatic HER2-positive cancer. Approval was based on results from the Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) trial. [28]

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. [28]

The CLEOPATRA trial compared first-line trastuzumab plus docetaxel (plus placebo) with 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. [28]

The phase II TRYPHAENA cardiac safety trial found low rates of symptomatic left ventricular systolic dysfunction (LVSD) in 225 patients with locally advanced, operable, or inflammatory HER2-positive breast cancer. who received pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens. [29]  

On long-term efficacy analysis of TRYPHAENA, 3-year Kaplan-Meier survival estimates for disease-free survival (DFS) were 87-90%, depending on the specific regimen used; progression-free survival (PFS) rates were 87-89%. During post-treatment follow-up, LVSD of any grade occurred in 2.8-5.4% of patients, and declines in left ventricular ejection fraction of 10% to < 50% occurred in 11.1-16% of patients. [30]

In September 2013, pertuzumab became the first medicine approved by the FDA for the neoadjuvant treatment of breast cancer. 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). [31]

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 pCR compared with 21.5% of patients treated with trastuzumab and docetaxel (n = 107) at the time of surgery. [32]  

Results on 5-year follow-up supported the primary endpoint of improved pCR when neoadjuvant therapy combines pertuzumab with trastuzumab and docetaxel, although confidence indices are large and overlapping. Additionally, the study results suggested that total pCR could be an early indicator of long-term outcome in early-stage HER2-positive breast cancer. [33]

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