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Genentech's Perjeta Approved as New Treatment in HER2 Breast Cancer


By Peter Winter
BioWorld Insight Editor

Just a couple of weeks after the FDA’s Oncologic Drugs Advisory Committee voted overwhelmingly in favor of supporting approval of Genentech Inc.’s supplemental biologics license application (sBLA) for Perjeta (pertuzumab) in neoadjuvant treatment of breast cancer, the FDA granted accelerated approval of the drug.

This was a month ahead of the PDUFA target date of Oct. 31. The Perjeta regimen is the first neoadjuvant treatment approved for women with high-risk, HER2-positive early breast cancer. Last year the drug was approved for the treatment of patients with metastatic HER2-positive breast cancer. (See BioWorld Today, July 12, 2012.)

Perjeta’s new use, the FDA said, 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 spread or of dying from the disease.

Up until recently, new agents for breast cancer have been approved first in metastatic cancer, with early stage use following years later, based on large randomized trials with prolonged follow-up. According to Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, “We are seeing a significant shift in the treatment paradigm for early stage breast cancer.”

Neoadjuvant treatment makes it possible for a doctor to quickly assess whether a medicine is effective, and could also reduce a tumor’s size and allow easier surgical removal. Neoadjuvant trials assess therapy delivered before surgery, and could expedite development and approval of treatments for early breast cancer.

South San Francisco-based Genentech, a unit of the Roche Group, supported its sBLA primarily on data from a Phase II study showing that nearly 40 percent of people receiving the combination of Perjeta, Herceptin (trastuzumab) and docetaxel chemotherapy had no evidence of tumor tissue detectable at the time of surgery (pathological complete response, or pCR).

The trial showed statistically significant improvements in pCR in patients receiving pertuzumab plus trastuzumab and docetaxel compared to patients receiving trastuzumab plus docetaxel. The subgroup of patients with hormone receptor-positive tumors showed less improvement compared to those with hormone receptor-negative tumors. Total pCR was improved by 17.8 percent compared to Herceptin and docetaxel alone. (See BioWorld Today, Sept. 13, 2013.)

A confirmatory trial, the FDA noted, for the accelerated approval is being conducted, and a full review of the data from the ongoing Phase III APHINITY study will be required for the accelerated approval to be converted to a full approval. APHINITY compares Perjeta, Herceptin and chemotherapy with Herceptin and chemotherapy for adjuvant (postsurgery) treatment in people with HER2-positive early stage breast cancer. More than 4,800 participants are enrolled in this trial, and results are expected in 2016.