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ISSUE 4 AUGUST
New drug

Fulvestrant

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Faslodex (AstraZeneca)
pre-filled syringes containing 250 mg/5 mL
Approved indication: advanced breast cancer
Australian Medicines Handbook section 14.4.2

Women with breast cancer that is hormone receptor positive are often given an anti-oestrogen, such as tamoxifen, as part of their treatment. Despite this treatment the cancer can still advance and metastasise. When this occurs the woman may be treated with an aromatase inhibitor such as anastrozole to further reduce the circulating oestrogen concentrations.

Fulvestrant offers another option for postmenopausal women with hormone receptor positive, locally advanced or metastatic breast cancer whose disease has progressed despite taking tamoxifen. It competitively binds to oestrogen receptors and leads to their down-regulation. Unlike tamoxifen, fulvestrant has no agonist activity at the oestrogen receptor.

Fulvestrant is formulated as an oily solution. There is a slow absorption after intramuscular injection so the peak plasma concentration is not reached for a week. Absorption continues for over a month and a steady state is reached after six injections at one-month intervals. The half-life is approximately 50 days. As fulvestrant is a steroid molecule it is mainly eliminated by metabolism. Less than 1% of the dose is excreted in the urine.

A double-blind trial compared fulvestrant and tamoxifen in 587 postmenopausal women with locally advanced or metastatic breast cancer. Their cancers were hormone receptor positive (or of unknown status) and they had not been recently treated with hormonal therapy. Approximately 33% of the women responded to treatment with a median time to progression of the cancer of 6.8 months with fulvestrant and 8.3 months with tamoxifen. After 31 months of follow-up, 48% of the fulvestrant group were dead compared to 43% of the tamoxifen group. Although the overall results favoured tamoxifen there was less difference in outcomes in women with hormone-receptor positive tumours.1

Two studies have compared monthly injections of fulvestrant with daily oral anastrozole in women with breast cancer that had progressed despite hormonal therapy. One of these studies was an open label trial which included some Australians among the 451 participants. After a median follow-up of 14.4 months the cancer had progressed in 82.4% of the women taking fulvestrant and in 83.4% of those taking anastrozole.2 The other study was a double-blind American trial involving 400 women. After a median follow-up of 16.8 months the cancer had progressed in 83.5% of the women taking fulvestrant and in 86.1% of those taking anastrozole.3

When the results of the two trials2,3 were combined the median time to progression was calculated to be 5.5 months with fulvestrant and 4.1 months with anastrozole. After a median follow-up of 27 months 74.5% of the fulvestrant group and 76.1% of the anastrozole group were dead. There was no significant difference in the median overall survival (27-28 months).4

The frequency of adverse reactions to fulvestrant and anastrozole is similar2,3 and neither drug has a greater effect than the other on the patient's quality of life. Commonly reported adverse events with fulvestrant include hot flushes, injection-site reactions, gastrointestinal upsets, bone pain and rashes. Thromboembolism has been reported, but as the risk of thrombosis may be increased in patients with breast cancer the association with fulvestrant is uncertain. The effect of fulvestrant on bone is unknown. It is also unknown if fulvestrant will be of benefit to women with an advanced cancer which has previously been treated with tamoxifen and has not responded to an aromatase inhibitor.

manufacturer declined to supply data

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

 

References

  1. Howell A, Robertson JF, Abram P, Lichinitser MR, Elledge R, Bajetta E, et al. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol 2004;22:1605-13.
  2. Howell A, Robertson JF, Albano JQ, Aschermannova A, Mauriac L, Kleeberg UR, et al. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol 2002;20:3396-403.
  3. Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S, et al. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol 2002;20:3386-95.
  4. Howell A, Pippen J, Elledge RM, Mauriac L, Vergote I, Jones SE, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma. A prospectively planned combined survival analysis of two multi center trials. Cancer 2005;104:236-9.