Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial

Abstract

A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk The objective of the current study was to confirm the superior PFS advantage for 103 fulvestrant versus anastrozole observed in the FIRST study, in a double-blind Phase 3 104 design. The population for FALCON were postmenopausal women with hormone 105 receptor-positive locally advanced or metastatic breast cancer who had not received 106 prior endocrine therapy, in order to avoid reducing efficacy of the control arm through 107 exposure to adjuvant endocrine therapy. 108 METHODS 109 Study design 110The Fulvestrant and AnastrozoLe COmpared in hormonal therapy Naïve advanced 111 breast cancer (FALCON) trial (Clinicaltrials.gov: NCT01602380) is a Phase 3 112 randomised, double-blind, double-dummy, international, multicentre study that 113 compared the efficacy and tolerability of fulvestrant with anastrozole in 114 postmenopausal women with histologically confirmed ER+ and/or PgR+ locally 115 advanced or metastatic breast cancer. 116 Ethical approval 117The study was conducted in accordance with the Declaration of Helsinki and 118International Conference on Harmonisation/Good Clinical Practice guidelines. An 119 Randomisation and masking 133Patients were randomised sequentially (1:1) to fulvestrant 500 mg or anastrozole 1 mg 134 using a computer-generated randomisation scheme and an integrated voice/web 135 response system. Patients were stratified at randomisation according to locally 136 advanced or metastatic breast cancer; prior or no prior treatment with chemotherapy 137 for locally advanced or metastatic breast cancer; and measurable or non-measurable 138 disease. 139Study drugs were labelled using a unique identifier linked to the randomisation 140 scheme. The active study drug and placebo for fulvestrant (pre-filled syringes) and 141 anastrozole (tablets) were identically packaged to maintain blinding. 142 progression. Safety and tolerability were assessed at each study visit, and for up to 8 154 weeks after the last fulvestrant/placebo injection. HRQoL questionnaires were 155 administered at baseline and at 3-monthly intervals. Following disease progression or 156 treatment discontinuation, HRQoL questionnaires will be administered at 6-monthly 157 until a final OS analysis. 158 Outcomes 159The primary endpoint of the study was to demonstrate the superior PFS of patients 160 treated with fulvestrant vs anastrozole. A progression event was determined based on 161 tumour assessments performed locally by each investigator, and was defined by 162Response Evaluation Criteria in Solid Tumours (RECIST) 1·1, or 163 surgery/radiotherapy for worsening of disease, or death from any cause. 164 OS and ORR were tested using a multiple ...

NCCN Guidelines Insights: Breast Cancer, Version 1.2017

“…84 Results from a recent phase III trial (FALCON) of first-line treatment with fulvestrant compared with anastrozole in women with metastatic ERpositive breast cancer demonstrated improved PFS with fulvestrant (at the higher dose, 500 mg) over anastrazole at a median follow-up of 25.0 months (16.6 vs 13.8 months; HR for progression or death, 0.797; 95% CI, 0.637-0.999). 85 Quality-of-life outcomes were similar between the groups, with the most common adverse effects being arthralgia (17% vs 10%) and hot flashes (11% vs 10%) for fulvestrant and anastrazole, respectively. 85 Importantly, patients in the FALCON trial had not received any prior endocrine therapy in any setting.…”

“…85 Quality-of-life outcomes were similar between the groups, with the most common adverse effects being arthralgia (17% vs 10%) and hot flashes (11% vs 10%) for fulvestrant and anastrazole, respectively. 85 Importantly, patients in the FALCON trial had not received any prior endocrine therapy in any setting.…”

Endocrine Therapeutic Strategies for Patients with Hormone Receptor-positive Advanced Breast Cancer

“…The median PFS was 16.6 months with fulvestrant versus 13.8 months with anastrozole (hazard ratio, 0.797; 95% CI, 0.637-0.999; p=0.0486). 29 Subgroup analysis showed improved PFS in fulvestrant-treated patients whose disease had not spread to the liver or lungs at baseline, indicating that fulvestrant would be a particularly advantageous option for patients with non-visceral disease whereas, for patients with visceral disease, outcomes were similar.…”

Cyclin-Dependent Kinase Inhibitor, Palbociclib – A New Drug for the Treatment of Metastatic Breast Cancer

“…Следовательно, устране-ние взаимодействия ER с эстрогенами, достигаемое за счет назначения тамоксифена или ингибиторов ароматазы, не всегда оказывается достаточным для угнетения активности данного рецептора. Появ-ление нового препарата -фулвестранта, действие которого основано на разрушении ER, позволило увеличить эффективность ГТ за счет устранения воз-можности коллатеральной активации ER [18].…”

“…Следовательно, устране-ние взаимодействия ER с эстрогенами, достигаемое за счет назначения тамоксифена или ингибиторов ароматазы, не всегда оказывается достаточным для угнетения активности данного рецептора. Появ-ление нового препарата -фулвестранта, действие которого основано на разрушении ER, позволило увеличить эффективность ГТ за счет устранения воз-можности коллатеральной активации ER [18].Следующий этап развития терапии ER-положи-тельного РМЖ -изменение представлений о самих принципах лечения этой группы опухолей. Еще в 1980-х годах предпринимались попытки увели-чить эффективность ГТ за счет ее комбинирования с другими противоопухолевыми препаратами -на тот момент онкологи располагали только цитостатически-ми средствами.…”