Researchers involved in an international randomized trial have reported that pertuzumab may add to the activity of Gemzar® (gemcitabine) for the treatment of platinum-resistant ovarian cancer. The details of this study appeared in an early online publication in the Journal of Clinical Oncology on November 9, 2009.[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 to test newer agents 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. Pertuzumab is classified as an 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. In a previous study, pertuzumab alone appeared to have activity in patients with advanced ovarian cancer who have received extensive prior therapy.

One hundred thirty patients with platinum-resistant ovarian cancer were randomly allocated to receive Gemzar alone or Gemzar plus pertuzumab. The addition of pertuzumab improved progression-free survival by 34%. The objective response rate was 13.8% for Gemzar plus pertuzumab versus 4.6% for Gemzar alone. An increased effect was noted in patients with LowHER3 mRNA expression.

Comments: These data suggest that pertuzumab has significant activity in ovarian cancer and that response may be predicted by HER3 RNA expression.

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