Pertuzumab lengthens survival in metastatic breast cancer [CLEOPATRA Trial]

1. Adding pertuzumab (Perjeta) to trastuzumab (Herceptin) and chemotherapy increased average overall survival by nearly 16 months in women with HER2-positive metastatic breast cancer.

2. The addition of pertuzumab increased progression-free survival by more than six months.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Breast cancer is the most common cancer in women and kills roughly 40,000 women per year in the United States. The overexpression of human epidermal growth factor receptor 2 (HER2) protein in a breast tumor is associated with a more aggressive cancer and worse prognosis. Fortunately, technological advancements have allowed physicians to develop targeted therapies that are specific to this mutant protein. Trastuzumab, or Herceptin, is an antibody designed to interfere with the HER2 receptor and was first approved in 1998. Pertuzumab, commercially known as Perjeta, is an antibody against a different portion of the HER2 receptor and received FDA approval in 2012. Preclinical data has suggested that combining pertuzumab and trastuzumab results in a stronger signal blockade and greater benefit than either antibody alone. In the CLEOPATRA trial, researchers evaluated this finding in a randomized, double-blind, placebo-controlled, phase 3 trial by adding pertuzumab to trastuzumab and docetaxel (a standard chemotherapy agent) for first-line treatment of women with HER2-positive metastatic breast cancer. Preliminary findings yielded promising results and the present work represents follow-up data at a median of 50 months.

Adding pertuzumab to a regimen of trastuzumab and chemotherapy was associated with a nearly 16 month increase in overall survival. Moreover, women who received pertuzumab experienced a 6 month increase in progression-free survival. Patients in the control group who later crossed over to receive pertuzumab were included in the control group analysis, such that effect estimates may be underestimated. This study evaluated patients with metastatic disease and cannot be applied to women with early-stage disease. Confirmation of the findings using long-term follow-up data would further support the addition of pertuzumab to the chemotherapeutic treatment regimen for metastatic HER2-positive breast cancers.

Click to read the study in NEJM

Relevant Reading: Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer

In-Depth [randomized controlled trial]: Women with HER2-positive metastatic breast cancer who had not previously received chemotherapy or anti-HER2 therapy were randomized to receive either a combination of pertuzumab, trastuzumab and docetaxel (n=402) or a placebo, trastuzumab and docetaxel (n=406) as part of the CLEOPATRA trial. Outcomes included overall survival, progression-free survival, duration of response and safety. Participants were followed for a median of 50 months.

Women randomized to pertuzumab had an increased median survival compared to controls (56.5 vs. 40.8 months, p<0.001). Median progression-free survival was 6.3 months longer in the pertuzumab group (18.7 vs. 12.4 months, p<0.001). Adverse events more common in the pertuzumab group were diarrhea, upper respiratory tract infection, pruritus (itching) and muscle spasm.

Image: PD

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