Double-Blind, Randomized Placebo Controlled Trial of Fulvestrant Compared With Exemestane After Prior Nonsteroidal Aromatase Inhibitor Therapy in Postmenopausal Women With Hormone Receptor–Positive, Advanced Breast Cancer: Results From EFECT

Chia, Stephen; Gradishar, William J.; Mauriac, L.; Bines, José; Amant, Frédéric; Federico, Miriam Hatsue Honda; Fein, Luis; Romieu, Gilles; Buzdar, Aman U.; Robertson, J. F. R.; Brufsky, Adam; Possinger, K.; Rennie, Pamela; Sapunar, Francisco; Lowe, Elizabeth S.; Piccart, Martine

doi:10.1200/jco.2007.13.5822

Cited by 465 publications

(223 citation statements)

References 30 publications

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“…The apparent sensitivity of MCF7-LTED cells to further antiestrogenic treatment such as fulvestrant (Santen et al, 2001;Chan et al, 2002;Martin et al, 2003) substantiates this theory, leading to the proposal of clinical trials including these treatments and/or growth factor signaling inhibitors. However, these approaches have shown limited efficacy; in fact, fulvestrant only elicits a response in approximately 7% of ERa-positive tumors that regrow under AI therapy, although its clinical use is justified based on a clinical benefit rate of 32% (Chia et al, 2008). On the other hand, trials with combinations of AIs and growth factor signal inhibitors have not improved outcomes in most cases , except for recent results on novel combinations that are still under research (Baselga et al, 2009;Johnston et al, 2009).…”

Section: Effect Of 17be2 Through Eramentioning

confidence: 99%

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

et al. 2010

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Endocrine therapies targeting the proliferative effect of 17b-estradiol through estrogen receptor a (ERa) are the most effective systemic treatment of ERa-positive breast cancer. However, most breast tumors initially responsive to these therapies develop resistance through molecular mechanisms that are not yet fully understood. The longterm estrogen-deprived (LTED) MCF7 cell model has been proposed to recapitulate acquired resistance to aromatase inhibitors in postmenopausal women. To elucidate this resistance, genomic, transcriptomic and molecular data were integrated into the time course of MCF7-LTED adaptation. Dynamic and widespread genomic changes were observed, including amplification of the ESR1 locus consequently linked to an increase in ERa. Dynamic transcriptomic profiles were also observed that correlated significantly with genomic changes and were predicted to be influenced by transcription factors known to be involved in acquired resistance or cell proliferation (for example, interferon regulatory transcription factor 1 and E2F1, respectively) but, notably, not by canonical ERa transcriptional function. Consistently, at the molecular level, activation of growth factor signaling pathways by EGFR/ERBB/AKT and a switch from phospho-Ser118 (pS118)-to pS167-ERa were observed during MCF7-LTED adaptation. Evaluation of relevant clinical settings identified significant associations between MCF7-LTED and breast tumor transcriptome profiles that characterize ERa-negative status, early response to letrozole and tamoxifen, and recurrence after tamoxifen treatment. In accordance with these profiles, MCF7-LTED cells showed increased sensitivity to inhibition of FGFR-mediated signaling with PD173074. This study provides mechanistic insight into acquired resistance to endocrine therapies of breast cancer and highlights a potential therapeutic strategy.

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Section: Effect Of 17be2 Through Eramentioning

confidence: 99%

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

et al. 2010

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“…Recently, the overall analysis from the EFECT trial demonstrated that fulvestrant and exemestane have comparable efficacy and tolerability in postmenopausal women with advanced breast cancer following non-steroidal AI failure [12].…”

Section: Discussionmentioning

confidence: 99%

“…Details of the study design and methodology of EFECT have been reported previously [12]. Briefly, EFECT (study code 9238IL/0048) is a randomised, double-blind, doubledummy, multicentre, Phase III trial comparing the efficacy and tolerability of fulvestrant versus exemestane in postmenopausal women with hormone receptor-positive, locally advanced or metastatic breast cancer.…”

Section: Patientsmentioning

confidence: 99%

“…All patients received corresponding placebo medication. Treatment continued until disease progression, death or any other event necessitating treatment withdrawal; patients were followed up until death [12].…”

Section: Treatmentmentioning

confidence: 99%

“…Thus, there is an increasing need for alternative and effective treatments that can be used after non-steroidal AI failure, particularly in patients with VM, who are generally considered difficult to treat. The Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomised, double-blind, multicentre, Phase III study comparing the efficacy and tolerability of fulvestrant versus exemestane in postmenopausal women with hormone receptor-positive advanced breast cancer who progressed or recurred after prior therapy with a non-steroidal AI (anastrozole or letrozole [Femara TM ]) [12]. EFECT, therefore, assesses any cross-resistance between non-steroidal and steroidal AIs, as well as any crossresistance between AIs and fulvestrant.…”

Section: Introductionmentioning

confidence: 99%

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Activity of fulvestrant versus exemestane in advanced breast cancer patients with or without visceral metastases: data from the EFECT trial

Mauriac

Romieu²,

Bines

2008

Breast Cancer Res Treat

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Purpose Patients with visceral metastases (VM: lung and/or liver metastases) are generally regarded as being less responsive to hormonal therapy, and chemotherapy often becomes the default treatment. This paper reports a subgroup analysis from EFECT (The Evaluation of Faslodex versus Exemestane Clinical Trial) examining the efficacy of fulvestrant and exemestane in patients with or without VM. Methods EFECT is a randomised, doubleblind, multicentre, Phase III trial in postmenopausal women with advanced breast cancer progressing or recurring after prior non-steroidal aromatase inhibitor therapy. Results Overall, approximately 57% of patients in EFECT had visceral involvement. Fulvestrant and exemestane demonstrated clinical benefit in 29.1% and 27.2% of patients with VM, respectively. Median duration of response was 13.5 vs 10.8 months and median duration of clinical benefit was 9.9 vs 8.1 months, respectively. Conclusions These results encourage the use of endocrine agents such as fulvestrant in treating patients with advanced breast cancer and VM.

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Lower-Dose vs High-Dose Oral Estradiol Therapy of Hormone Receptor–Positive, Aromatase Inhibitor–Resistant Advanced Breast Cancer

Ellis

Gao

Dehdashti

et al. 2009

JAMA

262

229

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Double-Blind, Randomized Placebo Controlled Trial of Fulvestrant Compared With Exemestane After Prior Nonsteroidal Aromatase Inhibitor Therapy in Postmenopausal Women With Hormone Receptor–Positive, Advanced Breast Cancer: Results From EFECT

Abstract: Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.

Cited by 465 publications

References 30 publications

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

Activity of fulvestrant versus exemestane in advanced breast cancer patients with or without visceral metastases: data from the EFECT trial

Lower-Dose vs High-Dose Oral Estradiol Therapy of Hormone Receptor–Positive, Aromatase Inhibitor–Resistant Advanced Breast Cancer

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