Trials Support Replacing Tamoxifen With Anastrozole at Two Years

Jane Salodof MacNeil

December 09, 2004

Dec. 9, 2004 (San Antonio) — Switching postmenopausal women to the aromatase inhibitor anastrozole after two years of adjuvant endocrine therapy with tamoxifen reduced the risk of breast cancer recurrence by 40% for more than 3,000 women in two clinical trials.

Based on an analysis of the pooled data, investigator Raimund Jakesz, MD, from Vienna Medical School in Austria, recommended switching comparable postmenopausal patients after two years of tamoxifen therapy. "Anastrozole is superior in terms of event-free survival and distant recurrence-free survival," he told attendees yesterday at the 27th annual San Antonio Breast Cancer Symposium.

The analysis combined outcomes for 2,262 women in the Austrian Breast and Colorectal Cancer Study Group (ABCSG-8) trial and for 962 patients in the German Adjuvant Breast Cancer Group's ARNO 95 trial. None of these breast conservation patients had undergone adjunctive chemotherapy, according to Dr. Jakesz.

After two years of tamoxifen therapy, the two trials randomized 1,606 patients to three more years on tamoxifen and 1,618 patients to three years of anastrozole therapy. All patients were hormone-receptor positive, either estrogen-receptor positive or progesterone-receptor positive or both. About three quarters of patients in both groups were node negative.

At 26 months of median follow-up, the three-year event-free survival rate was 92.7% for the patients receiving tamoxifen and 95.8% for those receiving anastrozole. By this point, there was a total of 177 events: 110 in the tamoxifen group and 67 in patients in the anastrozole group. Anastrozole was especially effective in preventing distant recurrences, with 46 such events reported vs 75 in patients receiving tamoxifen.

These differences were highly significant, according to Dr. Jakesz. The hazard ratio for event-free survival with anastrozole was 0.60 (P = .0009); for distant recurrence–free survival, the hazard ratio was 0.61. While anastrozole was more effective in patients with grade 1 to 2 tumors, he concluded that patients did better irrespective of prognostic factors.

In response to an audience question, however, Dr. Jakesz said the results for the German trial did not reach statistical significance by itself. This may have been because the ARNO population was slightly older, with an age limit of 75 years vs 60 years for the Austrian study. The German trial also accepted patients with grade 3 disease whereas the Austrian's upper limit was grade 2.

Dr. Jakesz said the combined trials show the superiority of anastrozole when introduced after two years but do not establish whether there is an additional benefit to using tamoxifen first.

More trials are needed, Dr. Jakesz said, seconding comments by Paul E. Goss, MD, PhD, of Harvard Medical School in Boston, who discussed aromatase inhibitor trials reported at the meeting, including the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

Despite generally superior results for aromatase inhibitors compared with tamoxifen, Dr. Goss said that many questions remain to be resolved, including optimal duration of therapy. Clinicians still do not know whether monotherapy or sequential or combined endocrine therapy is best, he noted, declaring additional trials are needed.

"The question of whether tamoxifen pre-primes the cells to make them sensitive to aromatase inhibitors needs to be answered," Dr. Goss said.

Some of these questions will be answered by ongoing trials, experts say, such as BIG-FEMTA, a four-group trial evaluating five years of tamoxifen vs five years of letrozole vs 2 years of letrozole followed by tamoxifen vs 2 years of tamoxifen followed by 3 years of letrozole therapy. Results of this and other trials are likely to help determine the optimal use of these agents in postmenopausal women.

AstraZeneca provided "a degreeof sponsorship toward running costs associated with this trial," according to a speaker disclosure statement.

27th Annual San Antonio Breast Cancer Symposium: Abstract 2. Presented Dec. 8, 2004.

Reviewed by Gary D. Vogin, MD

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