FDA Approves Neoadjuvant Pertuzumab for Early-Stage Breast Cancer

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On September 30, 2013, the FDA 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.

Phase II Trial

Pertuzumab’s accelerated approval for neoadjuvant treatment is based on a phase II study designed to measure pathologic complete response.1 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. ■


1. Gianni L, Pienkowski T, Im YH, et al: Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): A randomized multicenter, open-label, phase 2 trial. Lancet Oncol 13:25-32, 2012.