Fulvestrant May be FIRST for ER-Positive Advanced Breast Cancer Overall Survival

FIRST findings suggest fulvestrant may extend overall survival compared with anastrozole for treatment-naive oestrogen receptor-positive advanced breast cancer

medwireNews: Overall survival (OS) analysis from the phase II Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) suggests that the selective oestrogen receptor (ER) agonist may be superior to anastrozole for this outcome in women who have not previously been treated for advanced breast cancer.

At data cutoff, median OS was 54.1 months for the 102 patients with locally advanced or metastatic disease who were randomly assigned to receive open-label fulvestrant (500 mg on days 0, 14, 28 and every 28 days thereafter) compared with 48.4 months for 103 patients using anastrozole 1 mg/day, giving a significant hazard ratio of 0.70.

Fulvestrant also conferred significantly longer OS in patients analysed by age, dual positive status for ER and progesterone receptor, the presence or absence of visceral involvement, and prior receipt of chemotherapy.

“To our knowledge, this represents the first time an endocrine monotherapy has demonstrated improved efficacy compared with a third-generation [aromatase inhibitor]”, say Matthew Ellis, from Baylor College of Medicine in Houston, Texas, USA, and co-workers.

However, the authors caution in the Journal of Clinical Oncology that the study is small and was not originally designed to determine OS; moreover, not all patients contributed to data for the additional analysis.

They therefore recommend that the findings be considered “preliminary, but clinically relevant” until the results of the phase III Fulvestrant and Anastrozole Compared in Hormonal Therapy Naive Advanced Breast Cancer (FALCON) trial, which has used a strict definition of endocrine therapy-naive disease, are released.

The current study follows initial FIRST results indicating that fulvestrant was superior for the primary endpoint of clinical benefit rate (72.5 vs 67.0%), as well as progression-free survival (23.4 vs 13.1 months).

Noting promising preliminary trial findings for the cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib in this patient population, the team describes the treatment algorithm for ER-positive advanced breast cancer as being in a “state of flux”.

“Currently, it is rational to consider fulvestrant 500 mg as a first-line treatment option given the potential for survival benefits, particularly in settings where palbociclib is not available or palbociclib cost or adverse effects are a significant concern, and especially if these results are confirmed in FALCON”, conclude Matthew Ellis et al.

“These data also suggest that a first-line study of fulvestrant 500 mg with a CDK4/6 inhibitor versus fulvestrant 500 mg alone is a logical proposition that could lead to further prolonged [time to progression].”


Ellis MJ, Llombart-Cussac A, Feltl D, et al. Fulvestrant 500 mg versus anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall survival analysis from the phase II FIRST Study. J Clin Oncol 2015; 14 September. doi: 10.1200/JCO.2015.61.5831

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