Fulvestrant Best For Hormone Therapy-Naive Advanced Breast Cancer

Endocrine therapy-naive postmenopausal patients with advanced hormone receptor-positive breast cancer derive a significant progression-free survival benefit from fulvestrant versus anastrozole

medwireNews: FALCON trial results support the use of fulvestrant for postmenopausal breast cancer patients with hormone receptor-positive locally advanced or metastatic disease who are naïve to endocrine therapy.

The phase III study findings published in The Lancet demonstrate a significant gain in progression-free survival (PFS) with the selective oestrogen receptor degrader compared with the third-generation aromatase inhibitor anastrozole , at a median of 16.6 versus 13.8 months and a hazard ratio (HR) of 0.797.

Fulvestrant offered significantly better PFS than anastrozole in most subgroups, although there was no significant difference between the treatment arms for patients with non-measurable disease, patients without HR-positive disease at baseline and those who had previously received chemotherapy for locally advanced or metastatic disease.

In addition, fulvestrant use in patients with nonvisceral disease achieved a median PFS of 22.3 months versus 13.8 months with anastrozole, giving a significant HR of 0.59, whereas the corresponding values for those with visceral disease were 13.8 and 15.9 months and a nonsignificant HR of 0.99.

This “intriguing result” may provide “some indications when planning treatment for patient with de-novo disease”, writes commentator Massimo Cristofanilli, from Northwestern University in Chicago, Illinois, USA, in a linked article.

“The results of the FALCON [Fulvestrant and Anastrozole Compared in Hormonal Therapy Naive Advanced Breast Cancer] study suggest that individuals with de-novo stage IV disease are particularly sensitive to fulvestrant, but we should use caution in interpreting the data because this study was not powered to assess this question”, he says.

“It is possible that the presence of additional (visceral) metastasis indicates not only a more aggressive disease but also a larger tumour burden and heterogeneous oestrogen sensitivity, and for patients with visceral metastasis, a combination of fulvestrant and anastrozole might also be appropriate.”

Lead author John Robertson, from Royal Derby Hospital Centre in the UK, and team report that overall survival data are not yet mature.

Over a median of 14.7 months of fulvestrant therapy, 73% of 228 patients reported adverse events, as did 75% of 232 patients using anastrozole for a median of 13.9 months. Grade 3 or more severe side effects were reported by 22% of fulvestrant-treated and 18% of anastrozole-treated patients, and serious adverse events occurred in 13% of both treatment arms.

In all, 7% and 5% of patients discontinued their drug because of side effects, respectively, and there were no deaths considered causally related to the treatment.

“Collectively, the efficacy and tolerability findings support the clinical effectiveness of fulvestrant in this setting”, the investigators summarise.

They conclude: “Results from our study therefore add to the extensive data for the efficacy and safety of fulvestrant in patients with advanced breast cancer and consolidate evidence for superior efficacy for fulvestrant compared with anastrozole shown in FIRST .”


Robertson JFR, Bondarenko IM, Trishkina E, et al. Fulvestrant 500 mg versus anastrazole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet; Advance online publication 28 November 2016. DOI: http://dx.doi.org/10.1016/S0140-6736(16)32389-3

Cristofanilli M. Metastatic breast cancer: focus on endocrine sensitivity. Lancet; Advance online publication 28 November 2016. DOI: http://dx.doi.org/10.1016/S0140-6736(16)32418-7

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