CHICAGO—For postmenopausal women with ductal carcinoma in situ (DCIS), anastrozole is more effective than tamoxifen, has a more acceptable safety profile, and may be a preferable option for adjuvant treatment, a phase 3 study presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting concluded.
Compared with the standard 5-year treatment of tamoxifen, 10-year breast cancer-free survival rates were higher in the anastrazole group, 93.5% compared with 89.2%, in 3,077 survivors of DCIS who underwent lumpectomy plus radiation, said Richard G. Margolese, MD, a professor of surgical oncology at The Jewish General Hospital, McGill University, in Montreal, ON, Canada.
This is the first study to compare the two treatments in women with DCIS.
From January 2003 to June 2006, the NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-35 study randomly assigned 3,104 postmenopausal women with estrogen receptor or progesterone receptor-positive DCIS to receive either tamoxifen 20 mg/day (1,552 patients) or anastrozole 1 mg/day (1,552 patients), each given for 5 years. Patients were stratified by age, younger than 60 or 60 or older.
At a median follow-up of 9 years, 198 cases of breast cancer had occurred, 114 in the tamoxifen group and 84 in the anastrozole group (hazard ratio [HR]=0.73; P=0.03). Dr. Margolese said that a significant time-by-treatment interaction indicated that the effect was not evident until later in the study (P=0.02), and that there was a significant interaction between treatment and age group (P=0.04): the benefit of anastrozole was observed in women younger than 60.
“The better outcome in women less than 60 years of age is something we can’t explain very well,” he said, adding that this is a “stimulus for future research.”
A total of 495 disease-free survival events occurred, 260 in the tamoxifen group and 235 in the anastrozole group (HR=0.89; P=0.21). The 10-year point estimates for disease-free survival were 77.9% for tamoxifen-treated patients and 82.7% for those on anastrazole.
Of the 186 deaths, 88 occurred in the tamoxifen group and 98 in the anastrazole arm (HR=1.11; P=0.48). At 10 years, overall survival was 92.1% for tamoxifen and 92.5% for anastrazole. There were 8 deaths due to breast cancer in the tamoxifen group and 5 in the anastrazole group.
There were 63 cases of invasive breast cancer in the tamoxifen group and 39 in the anastrazole group (HR=0.61; P=0.02). There was a nonsignificant trend for a reduction in breast second primary cancers with anastrazole (HR=0.68; P=0.07).
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The average annual rate and number of uterine cancers in the tamoxifen arm was 17, compared with 8 in the anastrozole sarm (HR=0.47; 95% CI: 0.18, 1.15).
Generally, there were no significant differences in the toxicity profiles of these agents, including thromboembolic events, hot flashes, arthralgia, and myalgia. Anastrozole has “a very acceptable safety profile, more of a nuisance than any serious disease,” he said. Although patients in the anastrazole arm had a higher rate of bone fractures compared to tamoxifen, the difference was not statistically significant.
“Women with DCIS already have several great treatment options, and now they have one more,” stated ASCO Expert Don S. Dizon, MD, in a press release.
“Aromatase inhibitors offer important advantages, but patients and their doctors should still consider the full range of options, including tamoxifen or even foregoing adjuvant treatment, as every approach carries its own risks and benefits.”