ODAC Recommends Accelerated Approval of Pertuzumab for HER2-Positive, Early-Stage Breast Cancer
The U.S. Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 13 to 0, with one abstention, in favor of recommending accelerated approval of a pertuzumab (Perjeta) regimen for neoadjuvant treatment in patients with high-risk, HER2-positive, early-stage breast cancer. If approved, the regimen will be the first neoadjuvant breast cancer treatment approved in the United States and the first treatment approved based on pathologic complete response data.
Pertuzumab is already approved in the United States for the treatment of HER2-positive metastatic breast cancer. The pertuzumab application for neoadjuvant use follows a proposed new FDA pathway designed to more quickly bring promising medicines to people with earlier stages of breast cancer, where treatment may have a greater impact.
The ODAC recommendation was based on a review of results from NEOSPHERE and TRYPHAENA, two phase II studies of pertuzumab in high-risk, HER2-positive early-stage breast cancer, as well as on longer-term safety data from the phase III CLEOPATRA study of pertuzumab in HER2-positive metastatic breast cancer.
NEOSPHERE Study
The NEOSPHERE study is a randomized, multicenter, international phase II study that was conducted in 417 people with newly diagnosed HER2-positive, locally advanced, inflammatory, or early-stage breast cancer with tumors greater than 2 cm. Participants were randomly assigned to four study arms and received four cycles (12 weeks) of neoadjuvant treatment. The primary endpoint was pathologic complete response.
Treatment with pertuzumab, trastuzumab, and docetaxel chemotherapy significantly improved the rate of total pathologic complete response by 17.8% compared to trastuzumab and docetaxel alone (39.3% vs 21.5%, P = .0063).
TRYPHAENA Study
In the TRYPHAENA study, 225 patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer with tumors greater than 2 cm were randomly assigned to one of three neoadjuvant pertuzumab regimens. The primary endpoint was cardiac safety. Secondary endpoints included pathologic complete response.
No new or unexpected cardiac adverse events were observed in any of the study arms. Adverse events observed were consistent with those seen in previous studies of pertuzumab, trastuzumab, and chemotherapy, either in combination or alone.
The study was not powered to compare the three study arms. The rates of total pathologic complete response were 56.2% for pertuzumab, trastuzumab, and anthracycline-based chemotherapy, followed by pertuzumab, trastuzumab, and docetaxel; 54.7% for anthracycline-based chemotherapy, followed by pertuzumab, trastuzumab, and docetaxel; and 63.6% for the anthracycline-free arm (pertuzumab, trastuzumab, docetaxel, and carboplatin chemotherapy).
The FDA will make a decision on whether or not to approve pertuzumab for this use by October 31, 2013.
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®.
