Anastrozole

SAN ANTONIO -- The aromatase inhibitor anastrozole is markedly more effective and better tolerated than tamoxifen for adjunctive therapy in postmenopausal women with early-stage breast cancer.

Those were the major findings of the largest breast cancer treatment trial ever conducted. The study was reported at the annual breast cancer symposium sponsored by the San Antonio Cancer Institute.

After a median 30 months of treatment, there were 317 breast cancer relapses or deaths among women in the anastrozole (Arimidex) arm of the trial, compared with 379 in the tamoxifen arm and 383 in women on both agents. This equated to an overall 17% reduction in risk of disease recurrence in women on anastrozole, compared with those on tamoxifen.

The reduction in recurrence risk was 22% among women with confirmed hormone receptor--positive tumors, reported Dr. Michael Baum, professor emeritus of surgery at University College, London.

Despite these encouraging findings, Dr. Baum cautioned that further investigation is warranted before physicians should switch their breast cancer patients from tamoxifen to anastrozole.

The current study known as the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial, was sponsored by AstraZeneca Pharmaceuticals, maker of Arimidex. It was a double-blind randomized study involving 9,366 women with early operable breast cancer at 380 hospitals in 21 nations. After completing primary surgery and chemotherapy if prescribed, these women with generally good-prognosis breast cancers were randomized to 1 mg/day of anastrozole, 20 mg/day of tamoxifen, or both.

The combination arm was included to see if dual therapy provided additional efficacy over that of tamoxifen alone, long considered the standard adjunctive therapy in patients with early breast cancer. It did not in any respect.

A secondary end point in ATAC was the incidence of new contralateral breast cancers. The risk of this untoward event was 58% lower in the anastrozole group, compared with the tamoxifen group.

"In many ways this is the most remarkable finding at this early point in the study I'm sure you don't need reminding that tamoxifen in long-term follow-up studies can reduce the incidence of contralateral breast cancer by 50%. So that's an additional relative risk reduction of nearly 60% with anastrozole above and beyond 50%," he said.

The 0.1% incidence of endometrial cancer in the anastrozole arm of ATAC was one-fifth that seen in patients taking tamoxifen. Other adverse events that occurred significantly less frequently in women on anastrozole included deep vein thrombosis, vaginal bleeding, ischemic cerebrovascular events, and vaginal discharge. (See chart.)

Only two adverse events were significantly less common in tamoxifen-treated women. Fractures, mostly of the wrist, occurred in 5.8% of women on anastrozole but in only 3.7% on tamoxifen. And new-onset musculoskeletal disorders occurred an absolute 6.6% less frequently in the tamoxifen group.

"In looking at these data I couldn't help thinking that we might have a dream team by combining anastrozole and bisphosphonates," Dr. Baum observed.

Dr. Martine J. Piccart commented that despite the encouraging ATAC findings, it's not yet appropriate to switch the enormous number of patients with early breast cancer now on tamoxifen for adjuvant therapy over to anastrozole.

People need to wait for longer follow-up to identify the true balance between benefits and risks, said Dr. Piccart of the Jules Bordet Institute in Brussels.

Dr. Baum agreed. Particular attention during extended follow-up will be devoted to the issues of bone mineral density and cognitive function in the anastrozole-treated women. "We are somewhat concerned about cognitive function with long-term depletion of estrogen."

Clinical experience with anastrozole now approaches 500,000 patient-years. Anastrozole is already approved as first-line therapy in postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer, as well as for advanced disease in postmenopausal women with cancer progression following tamoxifen.

COPYRIGHT 2002 International Medical News Group
COPYRIGHT 2002 Gale Group