PathVysion Gene Test Added to Herceptin Labeling

October 1, 2002

ROCKVILLE, Maryland-The Food and Drug Administration has approved the inclusion of the PathVysion HER-2 DNA Probe Kit, a new genedetection test, in the labeling of Herceptin (trastuzumab, Genentech). PathVysion is made and marketed by Vysis, Inc., a subsidiary of Abbott Laboratories. It joins HercepTest (DAKO) as the second screening test listed in the Herceptin labeling.

ROCKVILLE, Maryland—The Food and Drug Administration has approved the inclusion of the PathVysion HER-2 DNA Probe Kit, a new genedetection test, in the labeling of Herceptin (trastuzumab, Genentech). PathVysion is made and marketed by Vysis, Inc., a subsidiary of Abbott Laboratories. It joins HercepTest (DAKO) as the second screening test listed in the Herceptin labeling.

Herceptin, a humanized monoclonal antibody, first won FDA approval in September 1998 for use with paclitaxel (Taxol) in the first-line treatment of women with metastatic breast cancer whose tumors overexpress the protein HER-2, which is a human epidermal growth factor. Multiple copies of the gene for HER-2 result in aggressive growth of tumor cells in about 25% to 30% of patients. Herceptin is also approved as a single agent in second- or third-line therapy of HER-2-positive patients with metastatic disease.

Studies have shown increased survival among HER-2-positive women treated with Herceptin, which demonstrates "the importance of identifying appropriate candidates for Herceptin therapy," noted Gwen Fyfe, MD, Genentech’s senior director of oncology, medical affairs.

The FDA has approved three HER-2 tests to determine which women might benefit from Herceptin treatment. HercepTest and Pathway (Ventana), which is not listed on the Herceptin labeling, both rely on immunohistochemistry (IHC) to assess the HER-2 receptor status of women. In contrast, PathVysion uses fluorescence in situ hybridization (FISH) to determine the number of copies of the gene that codes for HER-2.

FDA Approval

PathVysion received FDA marketing approval on the last day of 2001. The agency’s approval of Genentech’s application to include the new detection test in the Herceptin labeling came 8 months after the agency’s Oncologic Drugs Advisory Committee (ODAC) unanimously recommended that it do so.

During the ODAC meeting, Genen-tech presented two studies to support its request. The first, a concordance study between the FISH and IHC technologies, showed a concordance in a 1:1 population of 82% between PathVysion and the clinical trials assay.

The second study was a retrospective clinical outcomes examination, which used archival tissue from three Herceptin trials. It compared the response rate, time to progression, and survival of 96% of 799 patients who took part in the trials and for whom FISH results were obtained. Of the 163 patients who had one or two prior chemotherapy treatments and were FISH positive, 22% showed a clinical response vs no response for the FISH-negative patients.

Among the study’s 451 patients who had no prior chemotherapy, 30% of the FISH-positive patients treated with chemotherapy alone and 54% of those who received both chemotherapy and Hercep-tin showed a clinical response. Among the FISH-negative patients, the response rate was 38% for those getting only chemotherapy and 40% for those getting both treatments. Moreover, among the women who received Herceptin, the FISH-positive women did better than those who were FISH-negative in terms of time to disease progression and survival.