Current breast cancer clinical trials

Randomized clinical trials of aromatase inhibitors (AIs) in postmenopausal women with advanced disease have now demonstrated that, for the first time, an endocrine intervention has been identified with improved efficacy compared to tamoxifen. In the next few months, initial results are expected from the ATAC adjuvant trial comparing anastrozole versus tamoxifen versus the combination in invasive disease, and several additional studies are evaluating AIs following adjuvant tamoxifen. Other trials in noninvasive disease and the high-risk setting are being planned.

 

Margolese R. Rationale for proposed National Surgical Adjuvant Breast and Bowel Project (NSABP): DCIS Trial. Tamoxifen versus Arimidex® (anastrozole) in postmenopausal patients with Ductal Carcinoma In Situ. Poster, 2001 Miami Breast Cancer Conference. Full-Text

 

SELECT PUBLICATIONS

Baum M. Use of aromatase inhibitors in the adjuvant treatment of breast cancer. Endocrine-Related Cancer 1999;6(2):231-234. Full-Text

Buzdar A. An overview of the use of non-steroidal aromatase inhibitors in the treatment of breast cancer. Eur J Cancer 2000;36 Suppl 4:S82-4. Abstract

Goss PE, Strasser K. Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol 2001;19:881-94. Abstract

Harper-Wynne C, Dowsett M. Recent advances in the clinical application of aromatase inhibitors. J Steroid Biochem Mol Biol 2001;76:179-86. Abstract

Miles I et al. Neoadjuvant Arimidex or tamoxifen, alone or combined, for breast cancer (IMPACT): PgR-related reductions in proliferation marker KI67. Proc ASCO 2000;Abstract 360.

Mouridsen H et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: Results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001:2596-2606. Abstract

Nabholtz JM et al. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: Results of a North American multicenter randomized trial. J Clin Oncol 2000;18(22):3758-3767. Abstract

Trialists’ Group TA. Pharmacokinetics of anastrozole and tamoxifen alone and in combination during adjuvant endocrine therapy for early breast cancer in postmenopausal women: A subprotocol of the ‘Arimidex ® and Tamoxifen Alone or in Combination’ (ATAC) trial. Br J Cancer 2001;85(3):317-24. Abstract


Posters:

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THE ATAC TRIAL
I chair the steering committee of the ATAC trial and have seen this trial through from back-of-an- envelope discussions in a pub years ago to completing accrual of more than 9,300 patients in record time. It's an amazing international collaboration — particularly an Anglo-American collaboration. The interim analysis from the Data Monitoring Committee at the end of last year advised us that there was no excess of predetermined adverse events; in other words, the drugs and the combinations seem to be as safe as expected. There is something like 30,000 women-years of exposure to Arimidex, so we have a really good handle on its safety profile. We already know about the pharmacokinetics and pharmacodynamics of the inter-action of anastrozole and tamoxifen. We should be ready to present the initial data at the end of this year.

—Michael Baum, ChM, FRCS

ADJUVANT AROMATASE INHIBITOR TRIALS
I am impressed by the data from the large aromatase inhibitor trials in first-line metastatic breast cancer, and on that basis, we have the hypothesis that the same type of comparison in the adjuvant setting may have a similar or magnified outcome. But we will have to wait to see the data.

—Gabriel Hortobagyi, MD

PROPOSED NSABP DCIS TRIAL
The driving force of current research is to move away from the concept that DCIS is simply a surgical problem — and that if you obtain 10 mm margins, the patient is cured and no adjuvant therapy is needed. Even if we take out the index DCIS, the risk for these women to have another tumor in either breast in the future is at least as high or higher than the risk for women in the NSABP P-1 prevention trial. So, chemoprevention in DCIS is an important issue, and we need to find out how to do this best.
The ATAC trial, which has past accrual and is nearing analysis, will answer the question about anastrozole in invasive breast cancer. We need to ask the same question in noninvasive disease.

—Richard Margolese, MD

PROPOSED IBIS 2 PREVENTION TRIAL
This will be an international trial, and we have two good models for big multinational trials — the ATLAS trial of tamoxifen duration and the ATAC trial — which ran very similar treatment arms to IBIS 2. The entry criteria of IBIS 2 will be similar to IBIS 1, but restricted to postmenopausal women. We don’t use the Gail model. Family history is factored in, along with nulliparity and pathologic entities such as atypical hyperplasia and LCIS. We’re also adding a new category of women who have mammographic dysplasia covering 50 percent or more of their breasts. That links it in nicely with screening which is really where prevention belongs. Screening programs should not only detect small cancers, but also identify women at high risk and offer them preventative strategies. IBIS 2 is also going to have a DCIS component. The trial will enter 12,000 high-risk women and another 4,000 patients with DCIS.

—Jack Cuzick, PhD

TRIALS OF AROMATASE INHIBITORS AFTER TAMOXIFEN
We've got adjuvant studies that look at aromatase inhibitors given after tamoxifen. The question now is, are those studies going to be relevant anymore? Is it really the studies that use aromatase inhibitors up front that are going to be the ones we're interested in? We may have a whole group of large studies with interesting information that we may not use, because we won’t be giving the drugs that way anymore.

—Kathleen Pritchard, MD
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