Background: Many endometrial cancers express hormone receptors and may respond to hormonal therapy, but the impact on quality of life (QOL) is unclear. The aim of PARAGON is to investigate anastrozole, in patients (pts) with various ER/PR positive metastatic gynaecological cancers in a series of 7 individual phase 2 studies embedded in a basket protocol, with recruitment to the endometrial sub-group complete. Methods: Investigator initiated single arm, open label trial of anastrozole, 1 mg/d in pts with ER and /or PR positive hormone naive endometrial cancer. Pts 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. QOL was assessed using the EORTC QLQ-C30 at baseline, monthly for the first 3 months and then 3 monthly until PD. The proportion of pts whose score improved by ≥10-points (considered clinically relevant) was calculated for each QLQ-C30 subscale. Linear regression was used to compare the change in scores between pts who achieved a 3-month clinical benefit and those with PD. Results: Clinical benefit rate in 82 evaluable pts at 3 months was 44 % (95% CI:34-55%) with a RECIST partial response in 6 (7%). The median PFS was 3.2 months (95% CR: 2.8-5.4). Median duration of clinical benefit was 5.6 months. Treatment was well tolerated with toxicity as expected. Pts achieving a 3-month clinical benefit were significantly more likely than progressors to achieve clinically significant improvements in several QOL domains by 2 months including: emotional functioning (39 vs 6%:p = 0.002), cognitive functioning (45 vs 19%:p = 0.021), fatigue (47 vs19%:p = 0.015) and global health status (42 vs 9%:p = 0.003). Clinical benefit was associated with significantly improved mean change scores at 2-3 months compared to progressors for these domains as well as for social functioning, financial problems, pain, appetite loss and constipation. Conclusions: 44% of patients with ER/PR positive endometrial cancer derived clinical benefit from anastrozole, associated with a significant improvement in QOL. Clinical trial information: ACTRN12610000796088.