Fulvestrant in Women With Advanced Breast Cancer After Progression on Prior Aromatase Inhibitor Therapy: North Central Cancer Treatment Group Trial N0032

Ingle, James N.; Suman, Vera J.; Rowland, Kendrith M.; Mirchandani, D.; Bernath, Albert M.; Camoriano, John; Fishkin, Paul; Nikcevich, Daniel A.; Perez, Edith A.

doi:10.1200/jco.2005.04.1053

Cited by 131 publications

(82 citation statements)

References 14 publications

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“…The incidence of thromboembolic events was higher in patients receiving fulvestrant in this study (5.8 vs 3.3%), but not significantly so (PZ0.22). This apparent increase in thromboembolic events was not noted in the other phase III trials of fulvestrant (Howell et al 2002, Osborne et al 2002) and no thromboembolic events were reported in two recent phase II studies (Ingle et al 2004, Perey et al 2004. Three patients receiving fulvestrant withdrew because of a drug-related AE (cerebrovascular accident, deep vein thrombosis and pulmonary embolus (one patient each)).…”

Section: Tolerability Of Pure Oestrogen Antagonistsmentioning

confidence: 70%

“…Furthermore, a phase II trial has shown that of 67 patients who developed resistance initially to tamoxifen and then to an AI, 28.4% subsequently gained CB (CR C PR C SD R24 weeks) with fulvestrant (median treatment duration 3.8 months) (Perey et al 2004). Similarly, in another phase II trial of 77 patients with advanced breast cancer who had progressed on prior AI therapy (21 had also received tamoxifen), 32.5% gained CB with fulvestrant (Ingle et al 2004(Ingle et al , 2006. Additionally, in the compassionate-use programme, CB was achieved in patients who received fulvestrant after progression on prior endocrine therapies, including both AIs and SERMs (Petruzelka et al 2004, Steger et al 2005.…”

Section: Future Directionsmentioning

confidence: 99%

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Pure oestrogen antagonists for the treatment of advanced breast cancer

Howell¹

2006

Endocr Relat Cancer

108

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For more than 30 years, tamoxifen has been the drug of choice in treating patients with oestrogen receptor (ER)-positive breast tumours. However, research has endeavoured to develop agents that match and improve the clinical efficacy of tamoxifen, but lack its partial agonist effects. The first 'pure' oestrogen antagonist was developed in 1987; from this, an even more potent derivative was developed for clinical use, known as fulvestrant (ICI 182,780, 'Faslodex'). Mechanistic studies have shown that fulvestrant possesses high ER-binding affinity and has multiple effects on ER signalling: it blocks dimerisation and nuclear localisation of the ER, reduces cellular levels of ER and blocks ER-mediated gene transcription. Unlike anti-oestrogens chemically related to tamoxifen, fulvestrant also helps circumvent resistance to tamoxifen. There are extensive data to support the lack of partial agonist effects of fulvestrant and, importantly, its lack of cross-resistance with tamoxifen. In phase III studies in patients with locally advanced or metastatic breast cancer, fulvestrant was at least as effective as anastrozole in patients with tamoxifen-resistant tumours, was effective in the first-line setting and was also well tolerated. These data are supported by experience from the compassionate use of fulvestrant in more heavily pretreated patients. Further studies are now underway to determine the best strategy for sequencing oestrogen endocrine therapies and to optimise dosing regimens of fulvestrant. At present, and for the foreseeable future, fulvestrant is the only oestrogen antagonist with no agonistic effects licensed for the treatment of advanced breast cancer in postmenopausal women. Other similar oestrogen antagonists are undergoing research and development, with a few currently being evaluated in phase II trials.

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Section: Tolerability Of Pure Oestrogen Antagonistsmentioning

confidence: 70%

Section: Future Directionsmentioning

confidence: 99%

Pure oestrogen antagonists for the treatment of advanced breast cancer

Howell¹

2006

Endocr Relat Cancer

108

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“…Several clinical studies have shown similar efficacy for fulvestrant compared with AIs together with a consistently good tolerability profile (Howell et al, 2002(Howell et al, , 2004(Howell et al, , 2005Osborne et al, 2002;Robertson et al, 2003;Ingle et al, 2006;Gradishar et al, 2007;Chia et al, 2008). However, no clinical studies have been conducted that address the issues of effectiveness and cost effectiveness of different treatment sequencing options for women with HR þ advanced breast cancer -a very important question, given standard clinical practice for treating advanced breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Fulvestrant is licensed in the United Kingdom for the treatment of postmenopausal women with oestrogen-receptor positive, metastatic breast cancer whose disease has progressed or relapsed on or after previous antioestrogen therapy. Several clinical studies have confirmed that fulvestrant is at least as effective as AIs in the treatment of advanced breast cancer in patients with HR þ disease (Howell et al, 2002(Howell et al, , 2004(Howell et al, , 2005Osborne et al, 2002;Robertson et al, 2003;Ingle et al, 2006). In addition, clinical evidence shows that the addition of fulvestrant into a sequence of well-tolerated hormonal therapies can be undertaken without a detrimental effect on responses to subsequent treatments Howell et al, 2005).…”

mentioning

confidence: 99%

Economic evaluation of fulvestrant as an extra step in the treatment sequence for ER-positive advanced breast cancer

Cameron

Camidge

Oyee³

et al. 2008

Br J Cancer

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Drug therapies for advanced breast cancer in hormone-receptor-positive disease include both hormonal and chemotherapies. Current UK practice is to minimise toxicity by using sequential hormonal agents for as long as clinically appropriate. A Markov model was developed to investigate the cost effectiveness of different sequences of therapies, particularly exploring the effects of adding an additional hormonal agent, fulvestrant, to the treatment pathway. A systematic review was undertaken and a panel of seven UK oncologists validated assumptions used for treatment efficacy, treatment pathways and resources used. Fulvestrant was found to be a cost-effective treatment option when added to the treatment sequence as a second-or third-line hormonal therapy for advanced disease. For a cohort of 1000 patients, fulvestrant as a second-line hormone therapy provided an additional 47 life years and 41 quality-adjusted life years (QALYs), at an additional cost of d301 359. This equated to d6500 per life years gained and d7500 per QALY. When used as a third-line option, the fulvestrant arm was dominant providing an increase in health benefit of 27 QALYs for the whole cohort, at a mean overall cost reduction of d430 per patient. Sensitivity analyses showed these results to be robust, demonstrating that fulvestrant is an economically viable additional endocrine option in the United Kingdom for the treatment of hormone responsive advanced breast cancer.

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“…Unfortunately, treatment options are limited when patients experience either progression or recurrence on non-steroidal AIs. There have been limited data to support the activity of both fulvestrant and exemestane in this setting, suggesting a lack of cross-resistance between these treatments and the nonsteroidal AIs [7][8][9][10][11]. 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.…”

Section: Introductionmentioning

confidence: 99%

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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Fulvestrant in Women With Advanced Breast Cancer After Progression on Prior Aromatase Inhibitor Therapy: North Central Cancer Treatment Group Trial N0032

Abstract: Fulvestrant is a well-tolerated treatment and has efficacy against breast cancers that have progressed after therapy with a third-generation AI.

Cited by 131 publications

References 14 publications

Pure oestrogen antagonists for the treatment of advanced breast cancer

Pure oestrogen antagonists for the treatment of advanced breast cancer

Economic evaluation of fulvestrant as an extra step in the treatment sequence for ER-positive advanced breast cancer

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

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