Phase Ii Trial Of Anastrazole In Combination With Gefitinib In Women With Asymptomatic Mullerian Cancer.

5063 Background: Both the selective aromatase inhibitor, anastrazole, (Arimidex) and Gefitinib (Iressa), an oral epidermal growth factor receptor tyrosine kinase inhibitor have demonstrated modest single agent activity in the treatment of women with ovarian cancer. Preclinical studies studies demonstrate that interruption of both pathways simultaneously may be an effective therapeutic strategy. Methods: Open label phase II study performed in patients with recurrent Mullerian malignancy including ovarian, peritoneal or fallopian tube carcinoma. Eligible patients had tumors that were IHC + for expression of the estrogen and/or progesterone receptor. Additionally, patients must asymptomatic without an indication for immediate systemic chemotherapy, ECOG PS of = 1. Patients could have either measurable or evaluable disease or a rising CA-125, defined as a single value > 35 U/ml or 2 successively rising values with the most recent 3 times patient’s nadir value. Archived tumor samples were also sent for quantitative EGFR expression, but this was not an eligibility requirement. Treatment consisted of anastrazole 1mg po qd and Iressa 250mg po qd. Monthly follow-up included interim history, physical exam and CA-125, with radiologic evaluation q 3 months. Results: Thirty five women with a median age of 60 (range 40–79 years) were enrolled. Included were 30, 4, and 1 women with ovary, primary peritoneal and fallopian tube cancers, respectively. To date 23 women are evaluable for response and 7 patients remain on study. Best overall response of patients who have completed the study includes 1 CR, 0 PR, 14 SD. Median TTT was 68 days (range 19–261), with 8, 2, 1 patients with stable disease at = 3, = 6, and = 9 months, respectively. An additional two patients remain on study with SD > 9 months. Toxicity was tolerable, including mild fatigue, nausea, hot flashes, skin rash (gr 1:17 pts, gr 2:5 pts, gr 3:1 pt), stomatitis (gr 1:4pts), and diarrhea (gr 1:15 pts, gr 2:5pts, gr 3:1 pt). Conclusions: Anastrazole in combination with Iressa is a well-tolerated oral regimen with modest activity in women with recurrent/persistent Mullerian cancers. Exploratory analysis regarding EGFR expression, EGFR mutations and response are underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca