Perjeta First Drug Ever Approved for Neoadjuvant Breast Cancer Therapy

October 2013, Vol 4, No 8 - FDA Approvals, News & Updates

The US Food and Drug Adminis­tration (FDA) granted accelerated approval to pertuzumab (Perjeta; Gen­entech) as part of a treatment regimen for the neoadjuvant setting (ie, before surgery) for patients with HER2-positive early-stage breast cancer. This is the first time that the FDA approved a drug for the neoadjuvant treatment of patients with breast cancer.

Pertuzumab received FDA approval in 2012 for the treatment of patients with advanced or metastatic HER2-positive breast cancer. This new indication is for patients with HER2-positive, locally advanced, inflammatory or early-stage breast cancer (ie, tumor size of >2 cm in diameter or with positive lymph nodes) who are at high risk for recurrence, of having their cancer metastasize, or who are at high risk of dying from breast cancer.

Pertuzumab is indicated for use in combination with trastuzumab (Herceptin) and other chemotherapy before surgery and, depending on the treatment regimen used, may be followed by chemotherapy after surgery. After surgery, patients should continue to receive trastuzumab to complete 1 year of treatment.

This approval opens a new path for the FDA to approve therapies for early-stage breast cancer. “We are seeing a significant shift in the treatment paradigm for early-stage breast cancer,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the Center for Drug Evaluation and Research. “By making effective therapies available to high-risk patients in the earliest disease setting, we may delay or prevent cancer recurrences.’’

“This is a historic moment,” said Mikkael A. Sekeres, MD, Associate Professor at the Cleveland Clinic who served as the chairman of the FDA’s advisory committee, which voted unanimously to approve the drug.

In May 2012, the FDA issued a draft guidance about the use of pathologic complete response (pCR) as a new end point to support the accelerated approval of a drug for the neoadjuvant treatment of high-risk, early-stage breast cancer. The accelerated approval of pertuzumab for neoadjuvant treatment is based on a study specifically designed to measure pCR. The study included 417 patients with breast cancer who were randomly assigned to receive 1 of 4 neoadjuvant treatment regimens—trastuzumab plus docetaxel, pertuzumab plus trastuzumab and docetaxel, pertuzumab plus trastuzumab, or pertuzumab plus docetaxel. Approximately 39% of the patients receiving pertuzumab plus trastuzumab and docetaxel achieved pCR compared with approximately 21% of those who received trastuzumab plus docetaxel, a significant difference.

The confirmatory trial for this accelerated approval is being conducted in 4800 patients with HER2-positive breast cancer who had previous breast cancer surgery and are at high risk of recurrence. The results are expected in 2016.

The most common side effects reported with pertuzu­mab plus trastuzumab and docetaxel were hair loss, diarrhea, nausea, and a decrease in white blood cells. Other significant side effects included decreased cardiac function, infusion-related reactions, hypersensitivity reactions, and anaphylaxis. September 30, 2013