Long-Term Data Back Anastrozole Over Tamoxifen in Breast Cancer

Allison Gandey
December 17, 2007 (San Antonio) — Anastrozole (Arimidex, AstraZeneca) offers long-term efficacy over tamoxifen (Nolvadex, AstraZeneca), and the benefits of treatment are maintained long after therapy is completed, researchers report. The trial presented here at the 30th Annual San Antonio Breast Cancer Symposium is the longest follow-up to date after 5 years of upfront treatment with aromatase inhibitors.
With a median follow-up of 8 years, the results promote the use of anastrozole as initial adjuvant endocrine treatment for postmenopausal women with hormone receptor–positive breast cancer.
The updated data from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial will also appear today in an early online issue of the Lancet Oncology.
"We observed no excess fracture rate and no new morbidity or mortality concerns," chairman of the ATAC steering committee, John Forbes, MD, from the University of Newcastle, in New South Wales, Australia, told the meeting.
During the question period after the talk, Eric Winer, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, said: "The headline for this should read, 'No difference in survival'." Dr. Weiner suggested there is a need to pursue new avenues.
Responding to the comments, Dr. Forbes said that although he concurs that there is great value in pursuing new activities, it took 10 years before investigators observed a reduction in recurrence with tamoxifen. "While we didn't have a survival advantage here, we may or may not see one at the 10-year mark."
He added: "Different biologies require different strategies. We have to accept that."
Treatment Benefits Maintained Long After Therapy Completed
During an interview with Medscape Oncology, session comoderator Judy Garber, MD, from the Dana-Farber Cancer Institute, said she considers these long-term data exciting. "The clinical change of switching to anastrozole has already been adopted, and these results support that decision. The challenge now will be to decide whether to prescribe an aromatase inhibitor at diagnosis or whether to choose tamoxifen and switch later."
Dr. Garber pointed out that comparison trials have already begun, but the data are not yet mature.
Results from clinical trials comparing aromatase inhibitors with tamoxifen have confirmed that aromatase inhibitors offer significant efficacy and tolerability advantages during the treatment phase. Aromatase inhibitors are now recommended as adjuvant treatment for postmenopausal women with hormone receptor–positive early breast cancer.
Dr. Forbes and his team pointed out that limited evidence exists on whether efficacy benefits or adverse effects persist after 5 years of adjuvant treatment with an aromatase inhibitor, and this study aimed to address this.
The ATAC trial compared the safety and efficacy of tamoxifen with the aromatase inhibitor anastrozole and with the combination of both drugs. The follow-up included a total of 46,202 women-years of follow-up for patients receiving monotherapy — a 38% increase in years of follow-up over the previous analysis (median follow-up of 68 months).
In this randomized double-blind study, the investigators evaluated more than 6200 postmenopausal women with localized invasive breast cancer. The primary endpoint for the trial was disease-free survival, and the secondary endpoints were time to recurrence, incidence of new contralateral breast cancer, time to distant recurrence, overall survival, and death after recurrence.
At a median follow-up of 100 months, the researchers found that disease-free survival, time to recurrence, time to distant recurrence, and contralateral breast cancer were significantly better in the intent-to-treat and hormone receptor–positive populations.
For patients with hormone receptor–positive breast cancer, the disease-free survival hazard ratio (HR) was 0.85 (95% confidence interval [CI], 0.76 – 0.94; P = .003). The HR for time to recurrence was 0.76 (95% CI, 0.67 – 0.87; P = .0001), for time to distant recurrence was 0.84 (95% CI, 0.72 – 0.97; P = .022), and for contralateral breast cancer was 0.60 (95% CI, 0.42 – 0.85; P = .004).
Dr. Forbes told the meeting that the absolute differences in time to recurrence increased by 2.8% (anastrozole 9.7% vs tamoxifen 12.5%) at 5 years and by 4.8% at 9 years (anastrozole 17% vs tamoxifen 21.8%).
Recurrence rates remained significantly lower with anastrozole vs tamoxifen after treatment completion (HR, 0.75; 95% CI, 0.61 – 0.94; P = .01). The researchers observed fewer deaths after recurrence with anastrozole (n = 245) vs tamoxifen (n = 269), but this was not significant (HR, 0.90; 95% CI, 0.75 – 1.07; P = .20), and they saw no effect for overall survival. Overall survival was not significantly different with anastrozole (n = 472) vs tamoxifen (n = 477; HR, 0.97; P = .70).
The investigators reported that fracture rates were higher in patients receiving anastrozole vs those receiving tamoxifen during active treatment, but were not different after treatment was completed.
They noted no significant difference in risk for cardiovascular morbidity or mortality between the treatment groups — an area of concern for aromatase inhibitors.
"These data show long-term safety findings and establish clearly the long-term efficacy of anastrozole compared with tamoxifen as initial adjuvant treatment for postmenopausal women with hormone-sensitive early breast cancer," Dr. Forbes said. "And they provide statistically significant evidence of a larger carryover effect after 5 years of adjuvant treatment with anastrozole compared with tamoxifen."
The 10-year follow-up analysis is planned for 2010, when all patients will be more than 10 years past their date of randomization.
The trial was sponsored by AstraZeneca. Dr. Forbes has disclosed that he is on the Speaker Bureau for the company and for Novartis Oncology. A number of the other trialists have disclosed similar financial relationships with AstraZeneca.
30th San Antonio Breast Cancer Symposium: Abstract 41. Presented December 14, 2007.