FDA Approves Neoadjuvant Pertuzumab for Early-Stage Breast Cancer
The U.S. Food and Drug Administration (FDA) today granted accelerated approval to pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and docetaxel for patients with early-stage breast cancer in the neoadjuvant setting. Pertuzumab is the first FDA-approved drug for the neoadjuvant treatment of breast cancer.
Pertuzumab was approved in 2012 for the treatment of patients with advanced or late-stage HER2-positive breast cancer.
New Indication
Pertuzumab’s new indication is for patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (tumor > 2 cm in diameter or with positive lymph nodes) who are at high risk of having their cancer return or metastasize or of dying from the disease. It is to be used in combination with trastuzumab 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 1 year of treatment.
“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 FDA’s 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.’’
In May 2012, the FDA issued a draft guidance about the use of pathologic complete response, defined as the absence of invasive cancer in the breast and lymph nodes, as an endpoint to support accelerated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 FDA’s accelerated approval program, patients are provided access to promising drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted.
Phase II Trial
Pertuzumab’s accelerated approval for neoadjuvant treatment is based on a phase II study designed to measure pathologic complete response. 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 pathologic complete response, compared to about 21% of those 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 neutropenia. Other significant side effects included decreased cardiac function, infusion-related reactions, hypersensitivity reactions, and anaphylaxis.
The FDA reviewed pertuzumab’s use for neoadjuvant treatment under the agency’s priority review program, which provides for an expedited review of drugs that may offer major advances in treatment.
Pertuzumab is marketed by Genentech, a member of the Roche Group.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
