Pertuzumab approved for early stage breast cancer under accelerated review

Under priority review, FDA approved pertuzumab (Perjeta, Genentech, a member of the Roche Group) on September 30 as part of a complete treatment regimen for patients with early stage breast cancer before surgery.

Pertuzumab 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 length of survival.

Pertuzumab’s 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 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.

“[Pertuzumab] is a new drug that offers physicians and their patients with HER2-positive breast cancer another treatment alternative that may prove to be quite beneficial to certain individuals,” Formulary advisor James M. Wooten, PharmD, associate professor, department of medicine, section of clinical pharmacology, University of Missouri-Kansas City, said. “The exact place where this particular drug falls in the treatment armamentarium for breast cancer remains to be determined.”

FDA issued a draft guidance in May 2012 about the use of pathologic complete response (pCR), defined as the absence of invasive cancer in the breast and lymph nodes, as an end point to support accelerated approval of a drug for neoadjuvant treatment of high-risk, early stage breast cancer.

Pertuzumab’s accelerated approval for neoadjuvant treatment is based on a study designed to measure pCR. In the study, 417 participants 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. 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 Perjeta regimen is the first neoadjuvant breast cancer treatment to be approved in the United States, and the first treatment approved based on pCR data,” said Genentech spokesperson Krysta Pellegrino. “Perjeta is available as a neoadjuvant treatment option for people with high-risk, HER2-positive early breast cancer less than 16 months after being approved for metastatic disease. This is several years earlier than would be possible through traditional approval pathways. Treating people with breast cancer early, before the cancer has spread, may offer the best chance of preventing the disease from returning.”

Hair loss, diarrhea, nausea, and a decrease in infection-fighting white blood cells were the most common side effects reported in participants receiving pertuzumab plus trastuzumab and docetaxel. Decreased cardiac function, infusion-related reactions, hypersensitivity reactions, and anaphylaxis were other significant side effects. 

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 it in 2013, according to the National Cancer Institute. Almost 20% of breast cancers have increased amounts of the HER2 protein.