KIEL, Germany -- For postmenopausal early-stage breast cancer, switching to an aromatase inhibitor from tamoxifen after two or three years improved recurrence-free and overall survival, according to a meta-analysis.
KIEL, Germany, Nov. 17 -- For postmenopausal early-stage breast cancer, switching to an aromatase inhibitor from tamoxifen after two or three years improved recurrence-free and overall survival, according to a meta-analysis.
Patients who switched to Arimidex (anastrozole) had fewer disease recurrences (92 vs. 159 [5% versus 8%]) and deaths (66 versus 90 [3% vs. 5%]) than did those who remained on tamoxifen, the meta-analysis found. The benefit of switching drugs was evident irrespective of nodal or receptor status, previous chemotherapy, or tumor size.
The meta-analysis, which was funded by AstraZeneca, maker of Arimidex, emerged from three clinical trials, Walter Jonat, M.D., of the University of Kiel here, and colleagues, reported online in The Lancet Oncology.
They analyzed the Austrian Breast and Colorectal Cancer Study Group (ABCSG), Arimidex-Nolvadex (ARNO 95), and the Italian Tamoxifen Anastrozole (ITA) studies. In all the trials, postmenopausal women with histologically confirmed, hormone-sensitive early-stage breast cancer were randomized to 1 mg/day Arimidex (n=2,009) after two to three years of tamoxifen or to continue taking Nolvadex at a dose of 20 or 30 mg/day (n=1,997).
Data were analyzed with a stratified Cox proportional hazards model with the covariates of age, tumor size, nodal status, grade, surgery, and chemotherapy.
Compared with those continuing on tamoxifen, patients taking Arimidex had significant improvement in:
These results show that the clinical benefits in terms of event-free survival seen in individual trials for the patients who switched to Arimidex translate into a benefit in overall survival, the authors said. Furthermore, they added, disease-free and event-free survival, including the occurrence of contralateral breast cancer and distant metastases, were significantly better among those who switched.
As for safety and tolerability, overall, there were significantly fewer serious adverse events, drug-related adverse events, and withdrawals due to adverse events in patients treated with Arimidex compared with those give then full course of tamoxifen.
Although a detailed analysis of the safety profiles of the drugs was beyond the scope of the meta-analysis, the investigators said, the profiles in the individual studies were consistent with those reported previously, and no new safety issues were found within the context of switching therapy after two to three years.
"A lot of people have been waiting to see whether aromatase inhibitors will show a survival advantages, and I think these data will assure them that five years of tamoxifen is no longer the standard of care," Dr. Jonat said. "The best treatment for women with hormone sensitive early-stage breast cancer should include an aromatase inhibitor."
Whether aromatase inhibitors should be offered as initial adjuvant treatment, or after two or more years of tamoxifen remains uncertain as studies differ, the researchers wrote.
"Clearly real data from well-designed clinical trials are needed," they said. The data from the current study cover only the time of switched treatment and are thus not directly relevant to a prospective treatment strategy starting with tamoxifen and then switching, they added. However, the survival benefit from this analysis suggests that a tamoxifen induction period might be beneficial, despite the possibility of high relapse rates in the first two years. This issue will be resolved only by prospective analyses of treatment strategies, Dr. Jonat's team said.
In the past few decades, five years' adjuvant tamoxifen therapy after primary treatment has been the gold standard for treating postmenopausal women with hormone-sensitive early-stage breast cancer. However, American Society of Clinical Oncology guidelines, for example, now recommend that ideally, adjuvant hormonal treatment in such women should include an aromatase inhibitor as initial treatment or after tamoxifen.
Furthermore, the National Comprehensive Cancer Network guidelines recommend switching to Arimidex after an initial two to three years of tamoxifen, for a complete five-year course, and the St. Gallen expert consensus also supports the use of an adjuvant aromatase inhibitor, the researchers said.
"Our findings further challenge the existing standard clinical approach of five years of adjuvant tamoxifen therapy," Dr. Jonat said. The results of this study "confirm that clinicians should consider switching postmenopausal women who have taken adjuvant tamoxifen for two to three years to anastrozole," he concluded.
The meta-analysis was funded by AstraZeneca, maker of Arimidex. Statisticians from AstraZeneca and SKM analyzed all the data and AstraZeneca funded a medical writer to help with technical writing for the English language. Drs. Jonat, Raimund Jakesz, and Manfred Kaufmann reported having done research sponsored by AstraZeneca. Dr. Kaufmann has received honoria from AstraZeneca, Pfizer, and Novartis. Dr. Francesco Boccardo has received travel grants and honoraria from AstraZeneca. Dr. Michael Gnant has received research support, travel grants, and honoraria from Novartis, AstraZeneca, Pfizer, Roche, and Sanofi-Aventis. Co-author Mike Greenwood is an employee of AstraZeneca.