COMMENTARY

Bevacizumab Shows Activity in Rare Ovarian Cancer

Rachel N. Grisham, MD

Disclosures

June 17, 2013

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Hello. I am Rachel Grisham. I am an assistant attending physician of gynecologic medical oncology at Memorial Sloan-Kettering Cancer Center in New York. Welcome to this edition of Medscape Oncology Insights, presented in association with Memorial Sloan-Kettering Cancer Center. Here at the American Society of Clinical Oncology (ASCO®) 2013 Annual Meeting we have heard the results of practice-changing and provocative studies in gynecologic cancer. I am pleased to present preliminary findings of a retrospective study[1] of bevacizumab for the treatment of recurrent and persistent low-grade serous and serous borderline ovarian cancer.

Epithelial ovarian, primary peritoneal, and fallopian tube cancers are the fourth leading cause of cancer-related mortality in women. Last year more than 22,000 women were diagnosed with ovarian cancer and more than 15,000 women died of the disease. Serous ovarian cancer, the most common type of epithelial ovarian cancer, is classified using a 2-tiered grading system: high- vs low-grade serous disease. Low-grade serous ovarian cancer is rare, accounting for about 10% of serous ovarian neoplasms. The remainder of the cases are high-grade. Low- and high-grade serous ovarian cancers are 2 clinically, histologically, and molecularly distinct diseases.

Whereas alterations within the mitogen-activated protein (MAP) kinase pathways, such as KRAS and BRAF mutations, are prevalent in low-grade serous ovarian cancer, they are rare in high-grade serous ovarian cancer. Conversely, mutations in P53 are common in high-grade but rare in low-grade serous ovarian cancer. Patients with low-grade serous ovarian cancer commonly have a protracted clinical course with a median survival of more than 10 years, in contrast to patients with high-grade serous ovarian cancer, in whom the response rate to initial chemotherapy is typically 80%.

Bevacizumab Proves Active in Ovarian Cancer

Patients with low-grade serous ovarian cancer typically have very poor response rates to cytotoxic chemotherapy. Retrospective studies have shown a response rate of less than 5% to chemotherapy in both the new adjuvant and the recurrent setting for patients with low-grade serous ovarian cancer.[2,3]Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has shown promising results for treatment of epithelial ovarian cancer, either as a single agent or in combination with chemotherapy.

GOG170D[4] examined patients with 1 or 2 previous regimens who were treated with single-agent bevacizumab. A response rate of 21% was seen. Furthermore, Cannistra and others[5] reported a phase 2 study of single-agent bevacizumab in patients with up to 3 previous regimens and platinum-resistant disease, in which case a single response rate of more than 15% was seen.

In combination with chemotherapy, the phase 3 randomized OCEANS study, reported by Aghajanian and others,[6]compared patients treated with gemcitabine, carboplatin, and bevacizumab with those treated with carboplatin, gemcitabine, and placebo. Following 6-10 cycles of chemotherapy, patients were treated with maintenance bevacizumab or placebo. The objective response rate was 78.5% in the group on the bevacizumab regimen vs 57.4% in the chemotherapy-alone group. A statistically significant improvement was seen with the addition of bevacizumab.

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