Roxanne Nelson

September 29, 2009

September 29, 2009 (Berlin, Germany) — Adjuvant therapy with exemestane (Aromasin) appears to be more effective than tamoxifen in reducing disease recurrence in breast cancer patients, according to data presented here at the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress.

The conclusions come from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) study, the largest of 3 trials to compare the efficacy of an aromatase inhibitor with tamoxifen as initial endocrine therapy.

The analysis shows that in postmenopausal patients with early invasive hormone-receptor-positive breast cancer, initial adjuvant treatment with exemestane was superior to tamoxifen in improving disease-free survival and reducing disease recurrence.

"At 2.75 years, exemestane was associated with improved disease-free survival, time to distant metastasis, and recurrence-free survival," said lead author Cornelis van de Velde, MD, PhD, professor of surgery at Leiden University Medical Center in the Netherlands.

"The data are very impressive," said Chris Twelves, MD, clinical director and professor of clinical cancer pharmacology and oncology at the Institute of Cancer Therapeutics in West Yorkshire, United Kingdom. "This study is another demonstration of the superiority of [aromatase inhibitors], and does reinforce that we use them up front."

Analysis of TEAM Trial

The TEAM cohort consisted of 9779 postmenopausal patients with invasive estrogen-receptor-positive and/or progesterone-receptor-positive early breast cancer from 9 countries who were prospectively randomized to tamoxifen 20 mg/day or exemestane 25 mg/day. All patients had completed primary therapy of surgery and, if indicated, chemotherapy .

The original trial began in 2001, when the primary end point was disease-free survival. But in 2004, on the basis of results of the Intergroup Exemestane Study (IES), which showed a strong benefit for exemestane, the study was amended. All patients in the tamoxifen group were switched to exemestane at 2.5 to 3 years.

The modified study design, explained Dr. van de Velde, had 2 end points. The first compared disease-free survival in patients using either tamoxifen or exemestane for up to 2.75 years. The second end point compared disease-free survival in women using exemestane for 5 years with that in women using tamoxifen who switched to exemestane for a total of 5 years.

The current analysis focused on the first primary end point — disease-free survival after 2.75 years with tamoxifen or exemestane — with the censoring of events, said Dr. van de Velde.

Their results showed that, compared with tamoxifen, exemestane is associated with better disease-free survival (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.77 - 1.03; P = .12) and relapse-free survival (HR, 0.85%; 95% CI, 0.72 - 1.00; P = .056). Time to first distant metastasis was also better with exemestane (HR, 0.81; 95% CI, 0.67 - 0.98; P = .028).

Overall, there were 11% fewer cases of local recurrence, distant metastases, contralateral breast cancer, and deaths without disease relapse for patients in the exemestane group.

Discontinuation Rates Higher for Tamoxifen

In the TEAM study, a much higher rate of patients in the tamoxifen group discontinued their treatment (29.5%; n = 1434), than in the exemestane group (18.9%; n = 926). In addition, 754 tamoxifen patients made an early switch to exemestane.

"Discontinuation rates varied considerably by country, and this does deserve more attention," said Dr. van de Velde. "We need to inform patients of the side effects, but also the benefits of continuing their treatment. Noncompliance can confound the results of [aromatase inhibitor] trials."

There were no unexpected safety issues reported, but exemestane use was associated with significantly higher incidences of arthralgia, carpal tunnel syndrome, diarrhea, and hypercholesterolemia. The incidence rate for cardiac ischemia and infarction was similar between the groups.

IES Data Also Show Superiority

More data showing superiority of exemestane, but from a switching trial, come from a long-term follow-up of the IES, and were reported at the meeting by Charles Coombes, MD, PhD, FRCP, FMedSci, head of oncology at Imperial College in London, United Kingdom. Whereas the TEAM study set out to compare initial therapy with the 2 products, the IES compared switching to exemestane after 2 to 3 years of tamoxifen with staying on tamoxifen for the full 5 years. The new longer-term data confirm a significant 18% reduction in disease-free survival in the group that switched (HR, 0.82; P = .0009), and show a significant prolongation of overall survival, reducing the risk of dying by 14% (HR, 0.86; P = .04).

"These new longer-term follow-up data from the IES demonstrate a significant survival benefit for patients who switched to exemestane compared with those who stayed on tamoxifen," Dr. Coombes said in a statement. "These findings are important to patients and physicians alike, as they reaffirm their confidence in switching to exemestane after 2 to 3 years on tamoxifen."

The use of exemestane after 2 to 3 years of tamoxifen therapy in postmenopausal women with estrogen-receptor-positive early breast cancer is an approved indication in both the United States and Europe.

Both the TEAM and the IES studies were funded by Pfizer, the manufacturer of exemestane.

15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstracts 2BA (TEAM study) and 5010 (IES study). Presented September 22, 2009.

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