Pertuzumab (Omnitarg™) Demonstrates Activity in Refractory Ovarian Cancer According to results presented at the Chemotherapy Foundation Symposium XXII, the monoclonal antibody pertuzumab demonstrates anti-cancer activity in patients with ovarian cancer that has stopped responding to standard therapies.<1> Most patients with stage III or IV ovarian cancer ultimately relapse and develop refractory disease. There is a great need to develop novel treatments for patients with ovarian cancer and newer agents are tested in women with refractory disease. The human epidermal growth factor receptor (HER) pathways are the collection of several biologic pathways within a cell that are involved in regulating the replication of cells. Often, cancer cells over-express components of the HER pathways which results in unchecked cellular replication – the hallmark trait of cancer. Herceptin® is an agent that is approved by the Food and Drug Administration (FDA) for the treatment of breast cancer that over-expresses HER2. Research is continuing to evaluate agents that may stop the growth signaling of the HER pathway in order to prevent the spread of some cancers. Pertuzumab is a classified as a HER dimerization inhibitor and was developed by Genentech, which also developed Herceptin®. Dimerization is considered essential for signaling activity of all HER receptors and pertuzumab inhibits this activation. Studies are currently underway in cancer types where dimerization is implicated. A phase I study performed by researchers from Cedars-Sinai Medical center established a safe dose for pertuzumab and observed a partial response in a patient with pancreatic islet cell cancer and a patient with ovarian cancer.<2> The study recently presented at the Chemotherapy Foundation Symposium included 58 patients with ovarian cancer who were treated with pertuzumab. Patients had an average of 5 prior chemotherapy regimens. At the time of the symposium, results from 7 patients were presented. Of these 7 patients, 1 achieved a partial disappearance of cancer, 5 achieved disease stabilization, and 1 patient experienced a “mixed response”, in which some of the tumors were reduce in size, while some tumors increased in size. Pertuzumab was well tolerated, with the most common side effects being diarrhea and rash. It was concluded that pertuzumab appears to provide activity in patients with advanced ovarian cancer who have received extensive prior therapy. Future clinical trials are planned to evaluate pertuzumab in addition to chemotherapy, and to compare this combination to chemotherapy alone to evaluate the true clinical effectiveness of pertuzumab. Comments: It’s much too early to determine if this drug will play a significant role in the future treatment of ovarian cancer. However, it is encouraging to see this effort to develop new drugs for the treatment of ovarian cancer. References: <1> Aghajanian C, et al. Proceedings from the Chemotherapy Foundation Symposium XXII. New York, New York. Novermber 10-13, 2004. <2> Agus DB, Gordon MS, Taylor C, et al. Phase I clinical study of pertuzumab, a novel HER dimerization inhibitior, in patients with advanced cancer. Journal of Clinical Oncology. 2005; published ahead of print on Feb 7, 2005.
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