Activity of Fulvestrant 500 mg Versus Anastrozole 1 mg As First-Line Treatment for Advanced Breast Cancer: Results From the FIRST Study

Robertson, J. F. R.; Llombart-Cussac, Antonio; Rolski, Janusz; Feltl, David; Dewar, John; Macpherson, Euan; Lindemann, Justin P.O.; Ellis, Matthew J.

doi:10.1200/jco.2008.21.1136

Cited by 277 publications

(175 citation statements)

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“…In the first-line setting, fulvestrant was found to be as effective as anastrozole in terms of overall response (36.0% vs 35.5%; odds ratio, 1.02; 95% CI, 0.56-1.87; P=.947) in evaluable patients (n=89 for fulvestrant and n=93 for anastrozole). 82 An improved time to progression was seen with fulvestrant compared to anastrazole (median time to progression was 23.4 months for fulvestrant vs 13.1 months for anastrozole; HR, 0.63; 95% CI, 0.39-1.00; P=.0496). 83 This study also used a higher loading dose of 500 mg every 2 weeks for 3 doses and then a maintenance dose of 500 mg monthly.…”

Section: First-line Endocrine Therapy For Metastatic Hormone Receptormentioning

confidence: 91%

“…83 This study also used a higher loading dose of 500 mg every 2 weeks for 3 doses and then a maintenance dose of 500 mg monthly. 82 The median OS was observed to be longer in the fulvestrant group than in the anastrozole group (54.1 vs 48.4 months; HR, 0.70; P=.041). 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).…”

Section: First-line Endocrine Therapy For Metastatic Hormone Receptormentioning

confidence: 98%

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NCCN Guidelines Insights: Breast Cancer, Version 1.2017

Gradishar¹,

Anderson

Balassanian

et al. 2017

J Natl Compr Canc Netw

376

331

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These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org.

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Section: First-line Endocrine Therapy For Metastatic Hormone Receptormentioning

confidence: 91%

Section: First-line Endocrine Therapy For Metastatic Hormone Receptormentioning

confidence: 98%

NCCN Guidelines Insights: Breast Cancer, Version 1.2017

Gradishar¹,

Anderson

Balassanian

et al. 2017

J Natl Compr Canc Netw

376

331

View full text Add to dashboard Cite

show abstract

“…The most common AE reported with fulvestrant in the 347 FALCON study was arthralgia, which occurred at a numerically higher frequency to 348 that noted in the FIRST study (16·7% [38/228] and 9·9%, respectively); 14 respectively, vs letrozole alone in postmenopausal women who had not received prior 360 systemic treatment for advanced breast cancer. 23,24 Statistically significant 361 improvements in PFS were shown for palbociclib plus letrozole (HR 0·58; 95% CI 362 0·46-0·72; p<0·0001) in PALOMA-2, and ribociclib plus letrozole (HR 0·56; 95% CI 363 0·43-0·72; p=3·29 × 10 -6 ) in MONALEESA-2 vs letrozole alone.…”

Section: Page 17mentioning

confidence: 93%

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

et al. 2016

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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 ...

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“…However, it also appears that the recommended monthly doses of fulvestrant used clinically may be suboptimal and in fact actually enhance tumor growth in tumors with phase II resistance with physiologic estrogen present (45). A recent clinical study on metastatic breast cancer demonstrates that doubling the monthly dose of fulvestrant enhances antitumor activity (46). In a laboratory study, an antitumor dose of fulvestrant in athymic animals implanted Figure 7.…”

Section: Discussionmentioning

confidence: 99%

Raloxifene-stimulated experimental breast cancer with the paradoxical actions of estrogen to promote or prevent tumor growth: A unifying concept in anti-hormone resistance

Jordan¹,

Dardes

Johnson

et al. 2010

Int J Oncol

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Abstract.We have previously demonstrated that prolonged treatments with raloxifene (RAL) in vitro will result in phase II RAL resistance and RAL-induced tumor growth. Clinical interest prompted us to re-examine RAL resistance in vivo, particularly the effects of long-term treatments (a decade or more) on the evolution of RAL resistance. In this study, we have addressed the question of this being a reproducible phenomenon in wild-type estrogen receptor (ER)-positive human breast cell line MCF-7. MCF-7 cells cultured under estrogen-deprived conditions in the presence of 1 μM RAL for more than a year develop RAL resistance resulting in an independent cell line, MCF7-RAL. The MCF7-RAL cells grow in response to both estradiol E 2 and RAL. Fulvestrant (FUL) blocks RAL and E 2 -mediated growth. Transplantation of MCF7-RAL cells into athymic ovariectomized mice and treatment with physiologic doses of E 2 causes early E 2 -stimulated tumor growth. In contrast, continuous treatment of implanted animals with daily oral RAL (1.5 mg daily) causes growth of small tumors within 15 weeks. Continuous re-transplantation of the tumors growing in RAL-treated mice indicated that RAL stimulated tumor growth. Tumors in the untreated mice did not grow. Bi-transplantation of MCF7-E 2 and MCF7-RAL tumors into the opposing mammary fat pads of the same ovariectomized animal demonstrated that MCF7-E 2 grew with E 2 stimulation and not with RAL. Conversely, MCF7-RAL tumors grew with RAL and not E 2 , a characteristic of phase II resistance. Established phase II resistance of MCF7-RAL tumors was confirmed following up to 7 years of serial transplantation in RAL-treated athymic mice. The ER· was retained in these tumors. The cyclical nature of RAL resistance was confirmed and extended during a 2-year evolution of the resistant phases of the MCF7-RAL tumors. The MCF7-RAL tumors that initially were inhibited by E 2 grew in the presence of E 2 and subsequently grew with either RAL or E 2 . RAL remained the major grow stimulus and RAL enhanced E 2 -stimulated growth. Subsequent transplantation of E 2 stimulated tumors and evaluations of the actions of RAL, demonstrated robust E 2 -stimulated growth that was blocked by RAL. These are the characteristics of the antiestrogenic actions of RAL on E 2 -stimulated breast cancer growth with a minor component of phase I RAL resistance. Continuous transplantation of the phase I RAL-stimulated tumors for >8 months causes reversion to phase II resistance. These data and literature reports of the cyclical nature of anti-androgen/androgen responsiveness of prostate cancer growth, illustrate the generality of the evolution of antihormonal resistance in sex steroid-sensitive target tissues.

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Activity of Fulvestrant 500 mg Versus Anastrozole 1 mg As First-Line Treatment for Advanced Breast Cancer: Results From the FIRST Study

Abstract: First-line fulvestrant HD was at least as effective as anastrozole for CBR and ORR and was associated with significantly longer TTP. Fulvestrant HD was generally well tolerated, with a safety profile similar to that of anastrozole.

Cited by 277 publications

References 12 publications

NCCN Guidelines Insights: Breast Cancer, Version 1.2017

NCCN Guidelines Insights: Breast Cancer, Version 1.2017

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

Raloxifene-stimulated experimental breast cancer with the paradoxical actions of estrogen to promote or prevent tumor growth: A unifying concept in anti-hormone resistance

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