FDA Approves Pertuzumab for Neoadjuvant HER2-Positive Breast Cancer

October 1, 2013

The FDA today granted pertuzumab (Perjeta) accelerated approval for the treatment of patients with HER2-positive early stage breast cancer prior to surgery who are at high risk for recurrence or metastasis.

The US Food and Drug Administration (FDA) today granted pertuzumab (Perjeta) accelerated approval for the treatment of patients with HER2-positive early stage breast cancer prior to surgery who are at high risk for recurrence or metastasis. The drug is the first one approved in this neoadjuvant setting for breast cancer patients, according to the FDA announcement. Pertuzumab is to be used in combination with trastuzumab (Herceptin) and chemotherapy.

The accelerated approval is based on the results of two phase II trials, the 417-patient open-label NeoSphere (Neoadjuvant Study of Pertuzumab and Herceptin in an Early Regimen Evaluation) trial previously published in the Lancet and the three-arm 225-patient TRYPHAENA (Trastuzumab Plus Pertuzumab in Neoadjuvant HER2-Positive Breast Cancer) study presented at the San Antonio Breast Cancer Symposium in 2011.

The drug was approved based on a pathologic complete response endpoint. Last year, the FDA issued a draft guidance suggesting that this endpoint can be used in neoadjuvant early-stage high-risk breast cancer trials for accelerated approval. Pathologic complete response is defined by the FDA as “the absence of invasive cancer in the breast and lymph nodes.”

“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 in an FDA press release. “By making effective therapies available to high-risk patients in the earliest disease setting, we may delay or prevent cancer recurrences.”

In the NeoSphere trial, 39% of trial participants who received pertuzumab plus trastuzumab and docetaxel achieved pathologic complete response, while only 21% achieved pathologic complete response on the trastuzumab plus docetaxel regimen (P = .0063).

Pertuzumab is already approved as part of a combination regimen with trastuzumab and docetaxel for patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy. The drug is a monoclonal humanized antibody that works by blocking the interaction of HER2 with other HER family membrane proteins and prevents downstream signaling and slows tumor growth.

A large 4,800-patient trial testing pertuzumab plus trastuzumab and chemotherapy as adjuvant therapy for HER2-positive breast cancer is currently recruiting patients (NCT01358877). Patients will be randomized after surgery to either pertuzumab or placebo in addition to chemotherapy and trastuzumab to test whether the triple combination improves Invasive disease-free survival. The trial is scheduled to continue until 2023 and is coordinated by both Roche, the manufacturer of pertuzumab and trastuzumab, and the Breast International Group.