SILVER SPRING, Maryland—The FDA’s Oncologic Drugs Advisory Committee (ODAC) has unanimously recommended that the agency amend the labeling of Herceptin (trastuzumab, Genentech) to include a new gene-detection test to identify women with metastatic breast cancer who are likely to benefit from the therapy. The 16-to-0 vote backed adding the PathVysion HER-2 DNA Probe Kit to the labeling. The kit is made by Vysis, Inc., now owned by Abbott Laboratories.
The FDA approved Herceptin, a humanized monoclonal antibody, in September 1998 for use in combination with paclitaxel(Drug information on paclitaxel) (Taxol) as a first-line treatment for women with metastatic breast cancer whose tumors overexpress the protein HER-2, an epidermal growth factor receptor. The antibody is also approved as a single-agent therapy for HER-2-positive patients as second- and third-line therapy.
Currently, the FDA has approved two tests for selecting Herceptin patients, the HercepTest (DAKO, Inc.) and Pathway (Ventana, Inc.), although only the HercepTest is listed in the Herceptin package insert. Both tests rely on immunohistochemistry (IHC) to assess HER-2 status.
The PathVy-sion kit, on the other hand, uses fluorescence in situ hybridization (FISH), which can determine the number of HER-2 genes in a woman’s breast cancer cells. The gene codes for the HER-2 protein, and thus its amplification in a tumor cell can reveal a patient’s potential to respond to Herceptin therapy.
"A direct correlation exists between gene amplification and overexpression," said Michael Press, MD, PhD, professor of pathology, University of Southern California Norris Comprehensive Cancer Center. "Amplification, as determined by FISH, is a clinically meaningful measure associated with poor prognosis and predictive of therapeutic response."
Dr. Press described the biology of HER-2 and the ways to assess it on behalf of Genentech.
The sponsor presented two studies in support of adding PathVysion to the Herceptin package insert—a concordance study between the FISH test and the IHC test used as the Herceptin clinical trials assay and a clinical outcomes study that assessed FISH using archived tissue from Herceptin trials.
