Antiangiogenic therapy for granulosa cell tumors of the ovary

Abstract

5574 Background: Sex-cord stromal ovarian tumors (SCSTs) tend to respond poorly to chemotherapy agents. Therefore, we examined the clinical efficacy of bevacizumab with or without concurrent chemotherapy and evaluated the angiogenic characteristics of these patients’ tumors. Methods: We conducted an IRB-approved retrospective review of all patients with SCSTs seen at our institution from February 2004 to October 2008. Eligible patients underwent pathologic confirmation and clinical evaluation, and received bevacizumab. VEGF and CD31 immunohistochemical staining (IHC) was performed when tissue was available; microvessel density (MVD) was measured based on CD31 counts. Results: We identified 8 eligible patients treated with bevacizumab. Of these, 7 had adult granulosa cell tumors (GCT) and one had a juvenile GCT. Of the 8 patients, 4 had early stage disease (I or II), 2 had advanced stage disease (III), and 2 were unstaged. All patients were treated for recurrent disease and had been previously treated with cytotoxic chemotherapy, with a median of 3.5 prior regimens (range, 1–6). Of the 8 patients, one patient had a complete clinical response, 2 patients had a partial response, 2 patients had stable disease, and 3 patients progressed, yielding a response rate of 38% and a clinical benefit rate of 63%. The median progression-free survival (PFS) was 7.2 months and the overall survival (OS) was not reached at a median follow-up after starting bevacizumab of 23.6 months. Of the 8 patients, 5 had tissue available for IHC. VEGF expression was noted at some level in all samples; overexpression was present in 1 of the 5 patients (upper tertile of score), and moderate expression was observed in 3 of the 5 patients (middle tertile). VEGF overexpression correlated with shorter PFS (p = 0.006) and shorter overall survival (p = 0.02). High MVD (>12.3 per previous data based on ROC analysis) was present in 3 of the 5 patients, and correlated with VEGF overexpression (p = 0.007) and shorter overall survival (p = 0.004). Conclusions: Anti-VEGF therapy is highly effective in patients with ovarian granulosa cell tumors. On the basis of these observations, a prospective trial has now been initiated using single agent bevacizumab in patients with recurrent disease. No significant financial relationships to disclose.