FDA Approves Pertuzumab (Perjeta) for HER2-Positive Breast Cancer


Pertuzumab has been approved in combination with trastuzumab (Herceptin) and docetaxel chemotherapy for women whose breast cancer overexpress the HER2 receptor and who have not received prior systemic treatment.

Patients with HER2-positive breast cancer now have a new treatment option. Last week the US Food and Drug Administration (FDA) approved pertuzumab (Perjeta), a HER2-targeted antibody. The drug is approved in combination with trastuzumab (Herceptin) and docetaxel chemotherapy for women whose breast cancer overexpress the HER2 receptor and who have not received prior systemic treatment such as chemotherapy or trastuzumab monotherapy.

Approximately 20% of breast cancer patients have HER2-positive disease. The FDA estimates about 226,870 women will be diagnosed with breast cancer this year, including about 45,000 HER2-positive breast cancer patients.

Genentech had filed the combination therapy for a 6-month priority review process by the FDA after the results from the phase III, international randomized CLEOPATRA trial were presented in December of 2011 at the San Antonio Breast Cancer Symposium. The CLEOPATRA trial randomized 808 HER2-positive metastatic breast cancer patients to one of two arms as first-line treatment: pertuzumab plus trastuzumab and docetaxel, or a placebo plus trastuzumab and docetaxel.

Pertuzumab plus trastuzumab and docetaxel improved progression-free survival, the primary endpoint, by 6.1 months (P < .0001)-a median of 18.5 months, compared to 12.4 months in the standard combination arm. The median follow up was 19.3 months. Adding pertuzumab to standard treatment reduced the risk of disease worsening or death by 38%. The triple combination is the only regimen to show a significant improvement in progression-free survival as compared to trastuzumab plus chemotherapy as a first-line treatment in patients with HER2-positive metastatic breast cancer, according to the press release by Genentech. Trastuzumab plus chemotherapy was originally shown to increase both progression-free survival and overall survival.

“The data from CLEOPATRA were impressive showing a clinically meaningful improvement in progression-free survival, and even a trend for improved survival,” said Dr. Edith Perez, deputy director at the Mayo Clinic Cancer Center and professor of medicine in Jacksonville, Florida. Dr. Perez pointed out that because only 10% of patients on the trial received trastuzumab as an adjuvant treatment, the study population is “a bit different than those diagnosed with metastatic HER2-positive breast cancer today,” she said. Trastuzumab was approved as adjuvant therapy in 2006 before patients were enrolled in the CLEOPATRA trial.

The CLEOPATRA results were published in the New England Journal of Medicine earlier this year.[1] While mature overall survival data is expected in 2013, the authors indicate that there is a strong trend toward increased survival in the experimental, pertuzumab arm. Adding pertuzumab to the standard combination treatment was well tolerated among patients on the trial. A cardiac condition associated with trastuzumab, left ventricular systolic dysfunction did not increase in the experimental arm. Grade 3 toxicities were higher in the triple-therapy arm and included febrile neutropenia and diarrhea. Common toxicities seen in more than 30% of patients in the experimental arm included diarrhea, hair loss, low white blood cell count, nausea, fatigue, rash, and peripheral neuropathy.

Trastuzumab is a humanized monoclonal antibody that works by blocking HER2. Trastuzumab has been approved by the FDA since 1998. Pertuzumab also targets HER2 but binds a different region of the HER2 protein, according to Genentech. Pertuzumab prevents the HER2 receptor from dimerizing with other HER receptors (HER1, HER3, HER4) on the tumor cell membrane to prevent tumor growth and survival. Pertuzumab’s mechanism of action is believed to be complimentary to that of trastuzumab.

With the approval, Roche has agreed to post-marketing commitments related to the manufacturing process for pertuzumab. These include FDA review of data from the next several productions of the medicine. Dr. Perez highlighted that pertuzumab does not appear to work well as single agent but is best when combined with trastuzumab and chemotherapy. Prior to CLEOPATRA, earlier studies showed that pertuzumab did not show efficacy as a single agent in HER2-positive patients.

“Major improvements in therapy have translated into better patient’s lives, but more work still remains to be done,” said Dr. Perez.


Baselga J, Corts J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109-119.

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