COPENHAGEN, Denmark--Dako Corporations HercepTest was recommended unanimously for FDA approval by a joint committee of the Hematology and Pathology Devices Panel and Immunology Devices Panel, conditional on the company providing clear guidelines on how to conduct the test, so that laboratories can provide consistent results.
The new immunohistochemical test was designed specifically to identify patients with breast cancer whose tumor tissue overexpresses the HER2 protein. It is a result of an agreement announced last March in which Genentech, maker of Herceptin (trastuzumab), granted Dako a license, under its patent rights, to develop the test. A positive HercepTest result will aid in the assessment of patients with metastatic breast cancer for whom treatment with Herceptin is being considered. The Oncologic Drugs Advisory Committee (ODAC) has recommended that Herceptin receive FDA approval .
During the Herceptin clinical trials, it was determined that a simpler test was needed to identify patients who potentially could benefit from the agent. Dako proposed to the FDA to develop a test that, if successful, would reach or exceed a concordance level of 75% when compared to the immunohistochemical assay applied in the clinical trials for Herceptin. HercepTest exceeded its goal with a concordance of 79% that was shown to be reproducible in and between labs.
The test is based on a polyclonal antibody developed by Dako for specific detection of the HER2 protein. The antibody is applied to the tissue, and its binding is visualized to indicate the level of antigen in the tissue (figure). [An available HER2 test kit, Oncor Inc.s Inform, counts copies of the HER2 gene, rather than measuring the protein level.]
The Dako test is easy to conduct, since it requires relatively few steps and uses equipment routinely found in pathology laboratories. It requires about 3 hours to stain specimens of paraffin(Drug information on paraffin)-embedded tissue, which is then evaluated by the pathologist against a predetermined scoring system. (In the figure, the top two sample stains are rated negative and the bottom two are rated positive).