Drugs such as CDK4/6 inhibitors and PIK3CA inhibitors are now available in combination with hormonal therapy to circumvent resistance. We now have a greater understanding of resistance mechanisms. There have been major and transformative changes to the management of women with hormone receptor positive metastatic breast cancer in recent years.
PARAGON has answered a number of important questions regarding the potential role of aromatase inhibitors in ER/PR-positive gynaecological cancers.Īlthough the expression of these receptors is often high in many gynaecological cancers, the response rates are significantly lower than in breast cancer, which raises questions about mechanisms of resistance and importantly whether they can be overcome.
PARAGON TRIAL TRIAL
PARAGON was also the first prospective trial of hormonal therapy in low-grade serous cancer and confirmed the results of retrospective case series. What did PARAGON find?Ī key finding was that the objective response rates in cancers such as endometrial stromal sarcomas and granulosa cell tumours were much lower than suggested by the literature (which at the time was made up of retrospective case series and case reports). The basket design meant a single submission to an ethics committee and the potential to recruit many more patients to the study, which made it very attractive to centres. PARAGON demonstrated that it is possible to carry out trials in patients with uncommon / rare gynaecological cancers. PARAGON was the first prospective trial of hormonal therapy (anastrozole) in women with rare gynaecological cancers. All women had recurrent gynaecological cancers and shared one common feature: their cancers were oestrogen receptor (ER) and/or progesterone receptor (PR) positive and may therefore potentially respond to anti-oestrogens.