Fulvestrant (‘Faslodex’): Clinical experience from the Compassionate Use Programme

Steger, Guenther G.; Gips, Maya; Simon, Sérgio Daniel; Lluch, Aña; Vinholes, Jefferson; Kaufman, Bella; Wardley, Andrew M; Mauriac, L.

doi:10.1016/j.ctrv.2005.08.009

Cited by 24 publications

(24 citation statements)

References 10 publications

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“…In line with the present analyses, some endpoints favoured fulvestrant, with objective response rates of 15.7% and 13.2% and median durations of response of 17.5 months and 11.7 months for fulvestrant and anastrozole, respectively [6]. Furthermore, pooled data from a compassionate-use programme of 123 fulvestrant have reported CB in 32.4% of patients with VM [14]. Another compassionate-use study in Belgium has reported that 26.4% of patients with VM achieved CB following fulvestrant treatment [15].…”

Section: Discussionsupporting

confidence: 87%

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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Section: Discussionsupporting

confidence: 87%

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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“…A prospectively planned combined analysis demonstrated similar efficacy of the two drugs [23]. Those data were confirmed in a number of recently published observations [24][25][26].…”

Section: Introductionsupporting

confidence: 66%

“…As reported in other trials, fulvestrant treatment was associated with low incidence of grade III/IV toxicity [23][24][25][26]38]. One case of non-life threatening pulmonary embolism was observed, as well as a limited number of grade III joint pain, nausea, and hot flashes.…”

Section: Discussionmentioning

confidence: 54%

The Austrian fulvestrant registry: results from a prospective observation of fulvestrant in postmenopausal patients with metastatic breast cancer

Bartsch

Mlineritsch

Gnant

et al. 2008

Breast Cancer Res Treat

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International audienceEndocrine therapy is the preferred treatment in oestrogen- and/or progesterone-receptor (ER/PgR) positive breast cancer. Fulvestrant is a pure ER-antagonist. We present results from the Austrian Fulvestrant Registry. Three-hundred and fifty patients were included. Time to progression (TTP) was defined as primary endpoint. A multivariate analysis was performed to identify factors significantly associated with TTP. Fulvestrant was administered as first-line therapy in 26%, second-line in 49%, and third-line or beyond in 25%. TTP was median 7 months. We observed a response in 15% of patients and 41% had SD ≥ 6 months. First-line treatment and non-visceral metastases were associated with longer TTP. One case of pulmonary embolism was reported. Grade 3 toxicities consisted of joint pain (1.4%), nausea (1.4%) and hot flashes (0.3%). Fulvestrant was effective and well tolerated. TTP was superior to other trials, due to the large proportion of first-line patients. Activity is apparently independent of Her2-status

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“…It is likely that it is the latter activity which is responsible for the dramatic results observed in patients treated with faslodex who have failed at least one endocrine therapy and which has made it a first-in-class SERD approved for the treatment of metastatic breast cancer (16)(17)(18)(19). Although clinical studies have shown some success with faslodex, its poor pharmacodynamic properties and lack of oral bioavailability have limited its clinical utility (16)(17)(18)(19)(20). Thus, although faslodex has provided very important proof-of-concept information, it is clear that there is an unmet medical need for (a) faslodex-like compounds with improved pharmaceutical properties and (b) other SERDs/antiestrogens with distinct mechanisms of action.…”

Section: Introductionmentioning

confidence: 99%

Definition of Functionally Important Mechanistic Differences among Selective Estrogen Receptor Down-regulators

2007

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One subclass of antiestrogens, the selective estrogen receptor down-regulators (SERDs), have received considerable attention of late as they competitively inhibit estrogen binding and induce a rapid, proteasome-dependent degradation of the receptor. Contained within this class of molecules is the steroidal antiestrogen ICI182,780 (faslodex), recently approved for the treatment of metastatic cancer, and GW5638/DPC974, a SERD that is currently being evaluated in the clinic. Given that mechanistic differences between different selective estrogen receptor modulators have been translated into important clinical profiles, it was of interest to determine if the SERD subclass of ligands were likewise functionally or mechanistically distinguishable. In this study, we show that although the steroidal and nonsteroidal SERDs target ERA for degradation, the underlying mechanism(s) are different. Of note was the identification of a specific protein-protein interaction surface presented on ERA in the presence of the ICI182,780-activated receptor which is required for degradation. Interestingly, this surface is also presented on ERA in the presence of RU58,668, a SERD that is chemically distinct from ICI182,780. This surface is not required for GW5638-mediated degradation, and thus, this SERD seems to affect ERA downregulation by a different mechanism. These data suggest that sequencing of therapies using drugs of this class is likely to be possible. Finally, because of the unmet need for orally active SERDS that function similarly to ICI182,780, we have used the insights from these mechanistic studies to develop and validate a high-throughput screen for compounds of this class with improved pharmaceutical properties. [Cancer Res 2007;67(19):9549-60]

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Fulvestrant (‘Faslodex’): Clinical experience from the Compassionate Use Programme

Cited by 24 publications

References 10 publications

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

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

The Austrian fulvestrant registry: results from a prospective observation of fulvestrant in postmenopausal patients with metastatic breast cancer

Definition of Functionally Important Mechanistic Differences among Selective Estrogen Receptor Down-regulators

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