Pertuzumab combined with gemcitabine appears to provide an effective treatment combination for patients with recurrent platinum-resistant ovarian cancer. In a recent phase II study involving 130 patients, the combination of pertuzumab and gemcitabine offered increased treatment benefit over gemcitabine alone. Results were published in the Journal of Clinical Oncology.
Pertuzumab, called Omnitarg by Genentech, is a monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2) molecule, inhibiting its combination with other HER receptors, notably HER 3, and preventing tumor growth.
"Ovarian cancer has the highest mortality of all gynecologic cancers," says Sharmila Makhija, MD, first and corresponding author on the paper, director of gynecologic oncology at Emory University School of Medicine and a Georgia Cancer Coalition Distinguished Scholar. "We need to develop therapies with improved efficacy and fewer toxicities, especially for patients with platinum-resistant ovarian cancer who develop a resistance to standard chemotherapy."
Pertuzumab has shown activity in combination with trastuzumab in patients with HER2 positive metastatic breast cancer who did not respond to trastuzumab alone. Pre-clinical studies have also indicated that pertuzumab inhibits growth in ovarian, lung, breast and prostate tumor cells that do not over-express HER2. This is an important difference between pertuzumab and trastuzumab, which requires over-expression of HER2 to be effective.
Collaborators on the study included researchers from Genentech, South San Francisco; Sharp Rees-Stealy Medical Group, San Diego; Markey Cancer Center, University of Kentucky; University of Oklahoma Health Sciences Center; The Warren Alpert Medical School of Brown University; Dana Farber Cancer Institute; and Roche Diagnostics.
"The primary objectives of this study," says Makhija, "were to characterize the safety and to estimate progression free survival of pertuzumab with gemcitabine in patients with recurrent platinum-resistant ovarian, primary peritoneal, or fallopian tube carcinoma. In addition to the clinical benefit of pertuzumab seen in this group of ovarian cancer patients, a low HER3 mRNA expression was observed to potentially predict the clinical benefit of pertuzumab and may serve as a valuable prognostic marker in the future. Additional randomized studies will be required to further define the relationships between pertuzumab, HER3 and patient outcome."
The study was reported in Journal of Clinical Oncology Nov. 9, 2009, and supported by Genentech, South San Francisco.
Contact: Vincent Dollard
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