Paragon (Anzgog-0903): Phase 2 Study Of Anastrozole In Women With Estrogen Or Progesterone Receptor-Positive Platinum-Resistant Or -Refractory Recurrent Ovarian Cancer

Background: There is some evidence that a subset of patients with recurrent ovarian cancer may benefit from antiestrogen therapy. The Paragon study is a basket protocol that includes a series of phase 2 trials investigating the activity of anastrozole in patients with estrogen or progesterone receptor-Ypositive recurrent gynecological cancers. We report the results of treatment in patients with platinum-resistant or -refractory recurrent epithelial ovarian cancer.Methods: Postmenopausal women who had estrogen and/or progesterone receptor-Ypositive platinum-resistant or platinum-refractory recurrent ovarian cancer and disease measurable by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or GCIG (Gynecologic Cancer InterGroup) CA-125 criteria were eligible. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. The study was prospectively registered (ACTRN12610000796088).Results: There were 49 evaluable patients, and clinical benefit was observed in 13 (27%; 95% confidence interval [CI], 16%-Y40%). Therewere no complete or partial RECIST version 1.1 responses. Clinical benefitwas associated with higher global quality-of-life scores. Median progression-free survival was 2.7 months (95% CI, 2.0Y2.8 months). The median duration of clinical benefit was 2.8 months (95% CI, 2.6-Y5.7 months). Most patients (83%) progressed within 6months. Seven patients continued on treatment for longer than 6months. Anastrozole was well tolerated in most patients. Subgroup analysis suggested greater clinical benefit in patients with tumors with estrogen-receptor histoscore ofmore than 200, but this difference was not statistically significant.Conclusions: A subset of patients with estrogen-or progesterone-positive platinum-resistant or platinum-refractory recurrent epithelial ovarian cancers derives clinical benefit from anastrozole, with acceptable toxicity. The challenge remains how to identify them.