Anastrozole Approved for Use in Early Breast Cancer

October 1, 2002

The US Food and Drug Administration has approved anastrozole (Arimidex) for the adjuvant treatment of hormone-receptor-positive early breast cancer in postmenopausal women. The approval is based on research from the Arimidex,

The US Food and Drug Administration has approved anastrozole (Arimidex) for the adjuvanttreatment of hormone-receptor-positive early breast cancer in postmenopausalwomen. The approval is based on research from the Arimidex, Tamoxifen, Alone orin Combination (ATAC) study, which involved more than 9,300 postmenopausal womenin 21 countries. Anastrozole demonstrated a statistically significantimprovement in recurrence-free survival compared to tamoxifen.

"When the ATAC results were first announced, we knew thesewere important findings that had the potential to impact how breast cancer istreated," said principal US investigator Aman Buzdar, md, The University ofTexas M. D. Anderson Cancer Center, Houston. "With the approval of Arimidexin the adjuvant setting, women now have a treatment option other than tamoxifen."

Study Results

The results of the ATAC trial were first presented at the SanAntonio Breast Cancer Symposium in December 2001. Among the 3,125 women in theanastrozole group, 318 had a relapse of their breast cancer or died, comparedwith 379 of 3,116 women in the tamoxifen group (hazard ratio = 0.83; P = .01),representing a statistically significant 17% relative reduction in the risk ofdisease recurrence with anastrozole. The relative reduction in the risk ofrecurrence was 22% among women with confirmed hormone-sensitive tumors whoreceived anastrozole (217 of 2,617 women) vs tamoxifen (272 of 2,598 women;hazard ratio = 0.78).

The safety and tolerability of both anastrozole and tamoxifenwere evaluated in the ATAC trial in 3,093 patients taking tamoxifen and 3,092patients taking anastrozole. Venous thromboembolic events (including deep-veinthrombosis) were reported in 4% (n = 120) of patients taking tamoxifen comparedto 2% (n = 73) of anastrozole patients. Endometrial cancer occurred at a rate of0.5% (n = 15) among tamoxifen patients compared to 0.1% (n = 3) amonganastrozole patients. Vaginal bleeding was reported in 9% (n = 270) of tamoxifenpatients and 5% (n = 147) of anastrozole patients. Hot flashes were also morecommon among women treated with tamoxifen compared to those taking anastrozole—40%(n = 1,246) vs 35% (n = 1,082). Women taking anastrozole reported less vaginaldischarge and ischemic cerebrovascular events than women taking tamoxifen(vaginal discharge: 3% [n = 94] vs 12% [n = 378]; ischemic events: 1% [n = 40]vs 2% [n = 74]).

Angina pectoris was reported more frequently in anastrozole-treatedpatients (1.7%, n = 52) than in tamoxifen-treated patients (1%, n = 30); theincidence of myocardial infarction was comparable. Women taking tamoxifenreported fewer musculoskeletal disorders and fractures (including fractures ofthe spine, hip, and wrist) compared to the women taking anastrozole. Fractures(predominantly of the wrist) were reported in 5% (n = 145) of tamoxifenrecipients and 7% (n = 224) of anastrozole recipients. More patients receivinganastrozole were reported to have an elevated serum cholesterol compared topatients receiving tamoxifen (7% vs 3%).

Clinicians Advised to Discuss ATAC Results With Patients

Earlier this year, the American Society of Clinical Oncology (ASCO)issued guidelines on the use of aromatase inhibitors as adjuvant therapy forwomen with hormone-receptor-positive breast cancer. Overall, the panelconsidered the results of the ATAC trial and the extensive supporting data to bevery promising, and they encouraged physicians to discuss these results withtheir patients.

The committee felt that it was too early to recommend awholesale switch from standard use of tamoxifen in this setting and thatphysicians and patients need to reach their own conclusions after consideringall the available data. The panel also stated that anastrozole is the onlyaromatase inhibitor for which clinical trial data in the adjuvant setting areavailable, and it should be considered the preferred agent if an aromataseinhibitor is used in this setting.

The National Comprehensive Cancer Network (NCCN) updated theirbreast cancer guidelines in February 2002 to include information derived fromthe ATAC trial and also recommended that these results be discussed withpatients.

"The reason these guidelines are important topostmenopausal women with early breast cancer is that Arimidex gives them a newchoice," said Judy Perotti, committee member and director of PatientServices at Y-ME National Breast Cancer Organization. "The guidelines willhelp women and their doctors work together to determine the best treatmentoption."