Adjuvant anastrozole was at least as effective as tamoxifen in postmenopausal women with DCIS undergoing lumpectomy and radiotherapy, and may be more effective in select subpopulations, according to preliminary results of a clinical trial.
Dr. Richard G. Margolese
Richard G. Margolese, MD, CM, of the Jewish General Hospital and McGill University, Canada, presented Abstract LBA500 during the Breast Cancer—HER/ER Oral Abstract Session on Monday, June 1. The outcomes of the study indicated that anastrozole is a “preferable option for treatment of DCIS” because of its favorable safety profile and demonstration of effect among younger women in the study, he said.
“We now have another option for adjuvant therapy for DCIS. Patients can take tamoxifen or anastrozole, and if they’re in the right group, it might be preferable to take anastrozole,” Dr. Margolese said.
The NRG Oncology/NSABP B-35 study randomly assigned 3,104 patients to receive 20 mg per day of tamoxifen plus placebo or 1 mg per day of anastrozole plus placebo for 5 years; all patients received breast radiotherapy. Prior to being randomly assigned, patients were stratified by age younger or older than 60. The primary endpoint was breast cancer–free interval (BCFI).
Patient characteristics were balanced between the two groups. Although the population was predominantly white (87.4%), distribution by race was equivalent between the treatment groups.
Dr. Margolese said that there was no difference in BCFI between the two treatment groups until about month 96 of follow-up. At 10 years, 93.5% of women in the anastrozole group and 89.2% in the tamoxifen group remained disease free (hazard ratio [HR] 0.73; p = 0.03).
However, Dr. Margolese said, when the data were stratified by age there was a clear benefit for anastrozole among women younger than age 60 (Fig. 1). Although there was no difference in disease-free survival in the overall population (82.7% with anastrozole vs. 77.9% with tamoxifen; HR 0.89; p = 0.21), among women younger than age 60, anastrozole demonstrated a significant benefit: 88.8% remained disease-free compared with 81.5% of those who received tamoxifen (HR 0.69; p = 0.02). In contrast, the corresponding values among women older than age 60 were 77.3% and 74.8% in the anastrozole and tamoxifen arms, respectively (HR 1.03; p = 0.79). A similar pattern emerged during evaluation of several of the study’s secondary endpoints.
The better outcomes noted among women younger than 60 was “something we can’t explain very well,” Dr. Margolese said. Multivariate analysis considering body mass index, mortality by other causes, and compliance did not explain the difference in response by age, and the investigators are still looking for an explanation, he said.
Anastrozole demonstrated a favorable safety profile in the study. There were 17 and eight instances of uterine cancer in the tamoxifen and anastrozole groups, respectively, although there were more occurrences of osteopathic fractures with anastrozole (69 events) than with tamoxifen (50 events). Thromboembolic events were more frequent among patients treated with tamoxifen, Dr. Margolese said. Grade 0-1 hot flashes were commonly reported by patients in both groups, as were grade 0-2 arthralgia and myalgia.
Discussant Joseph Sparano, MD, of Montefiore Medical Center and Albert Einstein College of Medicine, noted that the data indicated anastrozole might be more effective in preventing ipsilateral recurrence and contralateral breast cancer events in women with DCIS. The trial is important, he said, because it was the first to compare anastrozole and tamoxifen head-to-head in postmenopausal women, and the suggestion of greater benefit among younger women is additive to previous findings in the literature.
“These findings support the theory that estrogen deprivation is more effective than the selective estrogen receptor modulator tamoxifen, including in younger women,” Dr. Sparano said.
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