Phase 2 study of anastrozole in recurrent estrogen (ER)/progesterone (PR) positive endometrial cancer: The PARAGON trial - ANZGOG 0903.

BACKGROUND:The clinical benefit rate with aromatase inhibitors and the impact of treatment on quality of life (QOL) in endometrial cancer is unclear. We report the results of a phase 2 trial of anastrozole in endometrial cancer. METHODS:Investigator initiated single-arm, open label trial of anastrozole, 1 mg/d in patients with ER and/or PR positive hormonal therapy naive metastatic endometrial cancer. Patients were treated until progressive disease (PD) or unacceptable toxicity. The primary end-point was clinical benefit (response + stable disease) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life (QOL) and toxicity. RESULTS:Clinical benefit rate in 82 evaluable patients at 3 months was 44% (95% CI: 34-55%) with a best response by RECIST of partial response in 6 pts. (7%; 95% CI: 3-15%). The median PFS was 3.2 months (95% CI: 2.8-5.4). Median duration of clinical benefit was 5.6 months (95% CI: 3.0-13.7). Treatment was well tolerated. Patients who had clinical benefit at 3 months reported clinically significant improvements in several QOL domains compared to those with PD; this was evident by 2 months including improvements in: emotional functioning (39 vs 6%: p = 0.002), cognitive functioning (45 vs 19%: p = 0.021), fatigue (47 vs 19%: p = 0.015) and global health status (42 vs 9%: p = 0.003). CONCLUSION:Although the objective response rate to anastrozole was relatively low, clinical benefit was observed in 44% of patients with ER/PR positive metastatic endometrial cancer and associated with an improvement in QOL.