The FDA ( Food and Drug Administration ) has granted accelerated approval to Perjeta ( Pertuzumab ) as part of a complete treatment regimen for patients with early stage breast cancer before surgery ( neoadjuvant setting ).
Perjeta is the first FDA-approved drug for the neoadjuvant treatment of breast cancer.
Perjeta was approved in 2012 for the treatment of patients with advanced or late-stage ( metastatic ) HER2-positive breast cancer. HER2-positive breast cancers have increased amounts of the HER2 protein that contributes to cancer cell growth and survival.
Perjetas new use is intended for patients with HER2-positive, locally advanced, inflammatory or early stage breast cancer ( tumor greater than 2 cm in diameter or with positive lymph nodes ) who are at high risk of having their cancer return or spread or of dying from the disease. It is to be used in combination with Trastuzumab ( Herceptin ) and other chemotherapy prior to surgery and, depending upon the treatment regimen used, may be followed by chemotherapy after surgery. Following surgery, patients should continue to receive Trastuzumab to complete one year of treatment.
In May 2012, the FDA issued a draft guidance about the use of pathologic complete response ( pCR ), defined as the absence of invasive cancer in the breast and lymph nodes, as an endpoint to support accelerated approval of a drug for neoadjuvant treatment of high-risk, early stage breast cancer. Under the FDAs accelerated approval program, patients are provided access to promising drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted.
Perjetas accelerated approval for neoadjuvant treatment is based on a study designed to measure pCR. In the study, 417 participants were randomly assigned to receive one of four neoadjuvant treatment regimens: Trastuzumab plus Docetaxel, Pertuzumab plus Trastuzumab and Docetaxel, Pertuzumab plus Trastuzumab or Pertuzumab plus Docetaxel. About 39% of participants who received Pertuzumab plus Trastuzumab and Docetaxel achieved pCR, compared to about 21% who received Trastuzumab plus Docetaxel.
The confirmatory trial for this accelerated approval is being conducted in participants with HER2-positive breast cancer who had prior breast cancer surgery and are at high risk of having their cancer return. More than 4,800 participants are enrolled in this trial, which will provide further data on efficacy, safety and long-term outcomes. Results are expected in 2016.
The most common side effects reported in participants receiving Pertuzumab plus Trastuzumab and Docetaxel were hair loss, diarrhea, nausea and a decrease in infection-fighting white blood cells. Other significant side effects included decreased cardiac function, infusion-related reactions, hypersensitivity reactions and anaphylaxis.
The FDA reviewed Perjetas use for neoadjuvant treatment under the agencys priority review program, which provides for an expedited review of drugs that may offer major advances in treatment.
Breast cancer is the second leading cause of cancer-related death among women. An estimated 232,340 women will be diagnosed with breast cancer, and 39,620 will die from the disease in 2013, according to the National Cancer Institute ( NCI ). Almost 20% of breast cancers have increased amounts of the HER2 protein. ( Xagena )
Source: FDA, 2013