Anti-tumor activity of letrozole in patients with recurrent advanced low malignant potential or low-grade serous ovarian tumors

Abstract

5582 Purpose: To evaluate the clinical activity of oral Letrozole in patients with recurrent and advanced low malignant potential or low grade serous ovarian tumors and to determine the impact of steroid receptor expression on this observed activity. Methods: In a phase II design, we recruited patients with confirmed recurrent advanced stage low malignant potential tumors and recurrent low-grade serous carcinomas. Measurable disease was required. Steroid hormone expression (ER and PR), EGFR, and Her2/neu expression were determined on available pathological material by IHC from the initial surgery or at documentation of recurrent disease and blood was obtained before enrollment and every other month while on therapy. Letrozole was administered orally at a dose of 2.5 mg once a day. The endpoints were objective response rate assessed by Response Evaluation Criteria in Solid Tumor. Adverse events were graded using the National Cancer Institute Common Toxicity Criteria. Results: Thirteen patients meeting eligibility have been enrolled are evaluable for response and toxicity. From objective clinical parameters (RECIST) no patients had a CR or PR; five patients (38%) had disease stabilizations, eight patients had progressive disease. However, using criteria for CA 125 response, we obtained a complete serologic response in 2 of 13 patients (15%), and a partial serologic response in 2 additional patients (15%); marker stabilization was seen in 5 other patients (38%). CA125 increased in four patients (31%). We also detected the presence of ER, PR, EGFR, Her-2/Neu by IHC, and estradiol in the plasma by ELISA. No significant correlation was observed between tumor marker response and ER expression alone. However, when we evaluated the co-expression of ER/PR we found 3 of 5 (60%) patients had a serologic response compared to just 1 of 8 patients with ER+/PR- tumors (P=0.07). We observed no severe adverse events. Conclusion: Our preliminary data suggests that oral Letrozole has some antitumor activity in recurrent advanced low grade or borderline ovarian tumors and is well tolerated. The analysis of correlation between objective response and combined prediction markers including phosphorylated ER, PR, AKT, and IGFR is ongoing (Supported by CTRF). No significant financial relationships to disclose.