FDA approves Perjeta for neoadjuvant breast cancer treatment
The FDA today granted accelerated approval to pertuzumab as part of a complete treatment regimen for patients with early-stage breast cancer in the neoadjuvant setting.
Pertuzumab (Perjeta, Genentech) was approved in 2012 for the treatment of patients with advanced or metastatic HER-2–positive breast cancer.
The FDA reviewed pertuzumab’s use for neoadjuvant treatment under the agency’s priority review program, which provides for an expedited review of drugs that may offer major advances in treatment.
The new designation is intended for patients with HER-2–positive, locally advanced, inflammatory or early-stage breast cancer (tumor >2 cm in diameter or with positive lymph nodes) who are at high risk for cancer metastasis or disease-related mortality.
Pertuzumab is intended to be used combined with trastuzumab (Herceptin, Genentech) and other chemotherapy prior to surgery and, depending upon the treatment regimen used, could be followed by chemotherapy after surgery. After surgery, patients should continue to receive trastuzumab to complete 1 year of treatment.
“We are seeing a significant shift in the treatment paradigm for early-stage breast cancer,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “By making effective therapies available to high-risk patients in the earliest disease setting, we may delay or prevent cancer recurrences.’’
In May 2012, the FDA issued a draft guidance regarding the use of pathologic complete response, defined as the absence of invasive cancer in the breast and lymph nodes, as an endpoint to support accelerated approval of a drug for neoadjuvant treatment of high-risk, early-stage breast cancer. Under the FDA’s accelerated approval program, patients are provided access to promising drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted.
Pertuzumab’s accelerated approval for neoadjuvant treatment is supported by a study designed to measure pathologic complete response. In the study, 417 participants were randomly assigned to one of four neoadjuvant treatment regimens:
- Trastuzumab plus docetaxel;
- Pertuzumab plus trastuzumab and docetaxel;
- Pertuzumab plus trastuzumab; and
- Pertuzumab plus docetaxel.
About 39% of participants who received pertuzumab plus trastuzumab and docetaxel achieved pathologic complete response vs. about 21% who received trastuzumab plus docetaxel.
The confirmatory trial for this accelerated approval is being conducted in participants with HER-2–positive breast cancers who had prior breast cancer surgery and are at increased risk of having their cancer return. More than 4,800 participants are currently enrolled in this trial, which will provide further data on efficacy, safety and long-term outcomes.
The most common adverse effects reported in participants receiving pertuzumab combined with trastuzumab and docetaxel were hair loss, diarrhea, nausea and a decrease in infection-fighting white blood cells. Other notable adverse effects included anaphylaxis, decreased cardiac function, infusion-related reactions and hypersensitivity reactions.