A phase 2 study of anastrozole in patients with oestrogen receptor and/progesterone receptor positive recurrent/metastatic granulosa cell tumours/sex-cord stromal tumours of the ovary: The PARAGON/ANZGOG 0903 trial

Gynecol Oncol. 2021 Oct;163(1):72-78. doi: 10.1016/j.ygyno.2021.07.024. Epub 2021 Aug 16.

Abstract

Background: Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs.

Methods: 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity.

Results: The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5-13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5-13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%-24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade.

Conclusions: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs.

Keywords: Aromatase inhibitors; Clinical benefit; Granulosa cell tumour ovary; Response.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anastrozole / therapeutic use*
  • Female
  • Granulosa Cell Tumor / chemistry
  • Granulosa Cell Tumor / drug therapy*
  • Granulosa Cell Tumor / mortality
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / chemistry
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Quality of Life
  • Receptors, Estrogen / analysis*
  • Receptors, Progesterone / analysis*
  • Sex Cord-Gonadal Stromal Tumors / chemistry
  • Sex Cord-Gonadal Stromal Tumors / drug therapy*
  • Sex Cord-Gonadal Stromal Tumors / mortality

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone
  • Anastrozole