Data From The Team Study Confirm Importance Of Aromasin® In Adjuvant Treatment Of Early Breast Cancer

Main Category: Breast Cancer
Article Date: 05 Jun 2007 - 1:00 PDT

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Data from the TEAM study have been announced today at ASCO, the world's largest cancer meeting. The findings, from the trial's endometrial sub-study, demonstrate that Pfizer's AROMASIN® (exemestane tablets) is five times less likely to cause endometrial thickening[i] - which can develop into cancer of the uterus lining[ii] - compared with tamoxifen, one of the most commonly prescribed breast cancer treatments, in postmenopausal women with hormone receptor positive breast cancer. Endometrial thickening can also cause vaginal bleeding and require intervention, significantly impacting on a woman's quality of life.

The TEAM (Tamoxifen, Exemestane, Adjuvant, Multicenter) trial is a randomized, multicenter trial of 9,487 patients, comparing 5 years adjuvant exemestane treatment versus 2-3 years adjuvant tamoxifen followed by exemestane for a total duration of 5 years in postmenopausal women with hormone receptor positive early breast cancer. The endometrial effects sub-study was based on an intent-to-treat population of 158 patients, of whom 65 were available for analysis in the tamoxifen arm, and 78 in the exemestane arm.1 The data being announced at ASCO are the first to be released from the endometrial sub-study of the TEAM trial, with highly-anticipated results from the core trial and other sub-studies to follow.

"Thickening of the endometrium can be the first stage of endometrial cancer, as well as causing other side-effects such as bleeding. This can be a concern when women take tamoxifen over an extended period," said Professor Dirk Kieback, Head of Department of Gynecology and Obstetrics, Helios-Klinikum Aue, Germany, and lead investigator of the TEAM endometrial sub-study. "Findings which show that Aromasin causes significantly less endometrial thickening are therefore very important, and provide physicians with data to support a treatment strategy which includes Aromasin."

The data from the TEAM endometrial sub-study reinforce earlier findings from the endometrial sub-study of the Intergroup Exemestane Study (IES), a landmark trial for exemestane Results of the IES demonstrated that endometrial thickening was significantly reduced in patients who switched to exemestane for 2-3 years after 2-3 years of tamoxifen, compared with patients who stayed on tamoxifen for the full 5 years of treatment.[iii] These data enable physicians to offer patients the early cardio- and bone-protective properties of tamoxifen while still gaining the endometrial and efficacy benefits of exemestane.

Results from the TEAM endometrial sub-study, measuring the endometrial effects of exemestane versus tamoxifen, demonstrate:

-- No cases of endometrial thickening >10mm in the exemestane arm compared with 11 in the tamoxifen arm (p=0.0001)1
-- 11 versus 34 cases of endometrial thickening >5mm in the exemestane and tamoxifen arms respectively (p<0.006)1
-- In total, endometrial thickening was observed 11 times in the exemestane arm versus 45 in the tamoxifen arm (p=0.0001)1
-- Time to endometrial thickening was significantly longer in the exemestane arm (p<0.0001), with an 84% risk reduction1
-- Increase in endometrial thickness from baseline to six months was 2.94mm (exemestane) versus 5.41mm (tamoxifen), and from baseline to 12 months was 2.64mm versus 6.0mm respectively (p<0.0006)1

Professor Kieback continued, "Aromasin has already proven to be a very effective adjuvant therapy for postmenopausal women with hormone receptor positive early breast cancer, demonstrating an overall survival benefit in the Intergroup Exemestane Study. Today's announcement confirms that it offers endometrial benefits, reinforcing its role as an important treatment option for this patient population."

The TEAM endometrial sub-study findings are the latest in a series of exemestane data emphasizing its benefits for postmenopausal women with hormone receptor positive early breast cancer:

-- In the IES, exemestane demonstrated an overall survival benefit ��" the only aromatase inhibitor to have done so in a large, randomised, multi-national, double-blind trial. The mature 55.7-month data, authored by Professor Charles Coombes et al. and published in The Lancet in February 2007, demonstrated that women who switched to exemestane after 2-3 years of tamoxifen experienced a 17% reduction in the risk of death, representing an overall survival benefit, compared with women who remained on tamoxifen for the full 5 years of therapy. The data also demonstrated that women who switched to exemestane experienced a 25% reduction in the risk of their cancer returning (p=0.0001) compared with those who continued on tamoxifen.[iv]

-- The B-33 trial[1] demonstrated the efficacy of exemestane in the extended adjuvant setting after 5 years of tamoxifen. The trial results show that postmenopausal women with hormone receptor positive breast cancer who received exemestane after 5 years of tamoxifen were 56% less likely to experience a relapse of breast cancer than those who received placebo (p=0.004).[v] Median follow-up of 30 months also showed that disease-free survival was improved by 32% (p=0.07).[vi] This evidence supports the potential benefits of switching tamoxifen patients to exemestane after 5 years.

-- Sub-protocols of the IES demonstrated that switching to exemestane has no adverse effect on quality of life;[vii] that exemestane was superior to tamoxifen in the reduction of endometrial thickening;3 and that on average, the overall 5 year effects on bone mineral density (BMD) of women switching from tamoxifen to exemestane are similar to the expected bone loss in a similar group of women without breast cancer.[viii]

About exemestane[ix]

Exemestane is currently indicated for the adjuvant treatment of postmenopausal women with estrogen receptor positive early breast cancer who have received 2-3 years of tamoxifen and are switched to exemestane for the completion of a total of 5 consecutive years of adjuvant hormonal therapy. Exemestane is also indicated for the treatment of advanced breast cancer in women with natural or induced postmenopausal states, whose disease has progressed following tamoxifen (US) / anti-estrogen (EU) therapy.

Exemestane should not be used in women who are premenopausal, are nursing or pregnant, have a known hypersensitivity to the drug, or are taking estrogen-containing agents. Exemestane should be used cautiously with drugs that are metabolised via CYP3A4 and have a narrow therapeutic window.9

Exemestane was generally well tolerated across all clinical studies; undesirable effects were usually mild to moderate. The withdrawal rate due to adverse events in studies was 6.3% in patients with early breast cancer receiving adjuvant treatment with exemestane following initial adjuvant tamoxifen therapy and 2.8% in the overall patient population with advanced breast cancer receiving the standard dose of 25 mg. In patients with early breast cancer the most commonly reported adverse reactions were hot flushes (22%), arthralgia (17%) and fatigue (17%). In patients with advanced breast cancer the most commonly reported adverse reactions were hot flushes (14%) and nausea (12%). Most adverse reactions can be attributed to the normal pharmacological consequences of estrogen deprivation (e.g. hot flushes).

Please see enclosed for full prescribing information.

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[i] Kieback DG et al. Endometrial effects of exemestane compared to tamoxifen within the TEAM trial: Results of a prospective randomized study. Abstract 527, presented Saturday 2 June at ASCO 2007
[ii] National Cancer Institute. www.cancer.gov/cancertopics/wyntk/uterus/page3. Last accessed 9 May 2007.
[iii] Bertelli G et al. Intergroup Exemestane Study: Results of the endometrial sub-protocol. Presented at the San Antonio Breast Cancer Symposium, December 2004
[iv] Coombes RC et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70
[v] Mamounas E et al, Benefit from exemestane (EXE) as extended adjuvant therapy after 5 years of tamoxifen(TAM): intent-to-treat analysis of NSABP B-33. Presentation, presented December 15, San Antonio Breast Cancer Symposium 2006
[vi] Mamounas E et al, Benefit from exemestane (EXE) as extended adjuvant therapy after 5 years of tamoxifen(TAM): intent-to-treat analysis of NSABP B-33. Abstract 49, presented December 15, San Antonio Breast Cancer Symposium 2006
[vii] Fallowfield LJ et al. Quality of Life in the Intergroup AROMASIN Study (IES) - a Randomized Trial of AROMASIN versus Continued Tamoxifen after 2-3 years of Tamoxifen in Postmenopausal Women with Primary Breast Cancer. Journal of Clinical Oncology. Vol 24, No 6, Feb 20, 2006
[viii] Coleman RE et al. Skeletal effects of exemestane in the Intergroup Exemestane Study (IES) two year bone mineral density and bone biomarker data. Presented on 10 December 2005, SABCS, USA
[ix] Aromasin prescribing information (Summary of Product Characteristics dated 24 August 2005)

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