Anthony Bonaventura1, Rachel L OʼConnell, Cristina Mapagu, Philip J Beale, Orla M McNally, Linda R Mileshkin, Peter T Grant, Alison M Hadley, Jeffery C H Goh, Katrin M Sjoquist, Julie Martyn, Anna DeFazio, James Scurry, Michael L Friedlander. 1. *Calvary Mater Newcastle, Newcastle; †National Health and Medical Research Council Clinical Trials Centre and ‡Westmead Institute for Medical Research, University of Sydney, Sydney; §Department of Gynaecological Oncology, Westmead Hospital, Westmead; and ∥School of Medicine, Western Sydney University; ¶Chris O'Brien Lifehouse; and #School of Medicine, University of Sydney, Sydney, New South Wales; **Royal Women's Hospital; ††University of Melbourne; ‡‡Division of Cancer Medicine, Peter MacCallum Cancer Centre; and §§Mercy Hospital for Women, Melbourne, Victoria; ∥∥Royal Brisbane and Women's Hospital and ¶¶School of Medicine, University of Queensland, Brisbane, Queensland; and ##Pathology North and ***Faculty of Health and Medicine, University of Newcastle, Newcastle; and †††Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
Abstract
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-positive 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-positive 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%-40%). There were no complete or partial RECIST version 1.1 responses. Clinical benefit was associated with higher global quality-of-life scores. Median progression-free survival was 2.7 months (95% CI, 2.0-2.8 months). The median duration of clinical benefit was 2.8 months (95% CI, 2.6-5.7 months). Most patients (83%) progressed within 6 months. Seven patients continued on treatment for longer than 6 months. Anastrozole was well tolerated in most patients. Subgroup analysis suggested greater clinical benefit in patients with tumors with estrogen-receptor histoscore of more 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.
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-positive 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-positive 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%-40%). There were no complete or partial RECIST version 1.1 responses. Clinical benefit was associated with higher global quality-of-life scores. Median progression-free survival was 2.7 months (95% CI, 2.0-2.8 months). The median duration of clinical benefit was 2.8 months (95% CI, 2.6-5.7 months). Most patients (83%) progressed within 6 months. Seven patients continued on treatment for longer than 6 months. Anastrozole was well tolerated in most patients. Subgroup analysis suggested greater clinical benefit in patients with tumors with estrogen-receptor histoscore of more 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.
Authors: Beryl L Manning-Geist; Sushmita B Gordhandas; Dilip D Giri; Alexia Iasonos; Qin Zhou; Jeffrey Girshman; Roisin E O'Cearbhaill; Dmitriy Zamarin; Stuart M Lichtman; Paul J Sabbatini; William P Tew; Karen Li; Autumn S McDonnell; Emeline M Aviki; Dennis S Chi; Carol A Aghajanian; Rachel N Grisham Journal: Gynecol Oncol Date: 2021-11-08 Impact factor: 5.304
Authors: Powel Crosley; Anniina Farkkila; Adrianne L Jenner; Chloé Burlot; Olivia Cardinal; Kyle G Potts; Kate Agopsowicz; Marjut Pihlajoki; Markku Heikinheimo; Morgan Craig; Yangxin Fu; Mary M Hitt Journal: Int J Mol Sci Date: 2021-04-29 Impact factor: 5.923
Authors: Susana Banerjee; Holly Tovey; Rebecca Bowen; Elizabeth Folkerd; Lucy Kilburn; Jennifer McLachlan; Marcia Hall; Nina Tunariu; Ayoma Attygalle; Joao Paulo Da Silveira Nogueira Lima; Sophie Perry; Peter Chatfield; Margaret Hills; Stan Kaye; Gert Attard; Mitch Dowsett; Judith M Bliss Journal: Ther Adv Med Oncol Date: 2020-12-29 Impact factor: 8.168