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Breast Cancer Home Page
NCI's gateway for information about breast cancer.
Drug Information Summaries
NCI's drug information summaries provide consumer-friendly information about certain drugs that are approved by the U.S. Food and Drug Administration (FDA) to treat cancer or conditions related to cancer.
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FDA Approval for TrastuzumabBrand name(s): Herceptin®
- Approved for HER2-overexpressing breast cancer
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.
On November 16, 2006, the U.S. Food and Drug Administration (FDA) granted approval to trastuzumab (Herceptin®, made by Genentech, Inc.) as part of a treatment regimen containing doxorubicin, cyclophosphamide, and paclitaxel for the adjuvant treatment of women with node-positive, HER2-overexpressing breast cancer. The approval is based on evidence of a significant prolongation in disease-free survival in women receiving trastuzumab and chemotherapy compared to those receiving chemotherapy alone.
An integrated interim analysis of 3752 women from two NCI-Cooperative Group trials (NSABP B31 and
NCCTG N9831) were reviewed. Both studies restricted enrollment to women whose breast cancer demonstrated 3+ overexpression of HER2 by immunohistochemistry or amplification of the HER2 gene by fluorescence in situ hybridization (FISH). All women received standard adjuvant chemotherapy [four 21-day cycles of doxorubicin and cyclophosphamide (AC) followed by paclitaxel administered weekly or every 3 weeks for a total of 12 weeks]. As appropriate, women also received hormonal therapy and local radiotherapy. Patients were randomly assigned to receive either no additional therapy or to receive trastuzumab at 4 mg/kg on the day of paclitaxel initiation and subsequently at 2 mg/kg weekly for a total of 52 weeks.
At the time of the interim analysis, there were 261 events among 1880 women in the chemotherapy alone arm and 133 events among 1872 women in the trastuzumab plus chemotherapy arm. The reduction in the risk of recurrence, second primary cancer or death was 52 percent (hazard ratio 0.48, 95 percent CI: 0.39; 0.59). An analysis of overall survival was conducted showing fewer deaths in the trastuzumab plus chemotherapy arm; however, the findings were not significantly different and were based on small number of deaths with 96 percent of the population alive.
The most serious trastuzumab toxicities were
The most common adverse reactions with trastuzumab were
- fever
- vomiting
- infusion reactions
- diarrhea
- infections
- increased cough
- headache
- fatigue
- dyspnea
- rash
- neutropenia
- anemia
- myalgia
Adverse reactions requiring trastuzumab interruption or discontinuation included severe infusion reactions, congestive heart failure, and significant declines in left ventricular cardiac function.
Serial measurement of left ventricular ejection fraction (LVEF) was obtained in the two clinical trials. Six percent of patients were unable to receive trastuzumab following completion of AC chemotherapy due to cardiac dysfunction (LVEF 50 percent or 15 point decline in LVEF from baseline to end of AC).
Following initiation of trastuzumab therapy, the incidence of new-onset, dose-limiting myocardial dysfunction was higher among patients receiving trastuzumab and paclitaxel as compared to those receiving paclitaxel alone. Of those patients with normal LVEF prior to initiation of trastuzumab/paclitaxel, 16 percent discontinued trastuzumab therapy due to clinical evidence of myocardial dysfunction or significant declines in LVEF. Approximately 2 percent in the trastuzumab plus chemotherapy arm and 0.4 percent in the chemotherapy experienced clinically symptomatic, laboratory-confirmed cardiomyopathy determined by an external review committee. One death was observed among 32 trastuzumab-treated patients with clinical evidence of cardiomyopathy. Among the 31 surviving patients, all were receiving cardiac medication at last follow-up and approximately half had evidence of recovery to a normal LVEF (defined as 50 percent) on continuing medical management.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products, or Patricia Keegan, M.D., director of the FDA's Division of Clinical Trials Design and Analysis.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other
products. (See "Understanding the Approval Process for New Cancer Treatments.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.
For further information related to oncology drug approvals, regulatory information and other oncology resources, please refer to the FDA's Oncology Tools Web site.
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