Paragon (ANZGOG-0903): Phase 2 Study of Anastrozole in Women With Estrogen or Progesterone Receptor-Positive Platinum-Resistant or -Refractory Recurrent Ovarian Cancer

Int J Gynecol Cancer. 2017 Jun;27(5):900-906. doi: 10.1097/IGC.0000000000000978.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anastrozole
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Carcinoma, Ovarian Epithelial
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Organoplatinum Compounds / pharmacology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Prospective Studies
  • Quality of Life
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Tissue Array Analysis
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*

Substances

  • Antineoplastic Agents, Hormonal
  • Nitriles
  • Organoplatinum Compounds
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Triazoles
  • Anastrozole

Associated data

  • ANZCTR/ACTRN12610000796088