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Anastrozole, tamoxifen demonstrate similar efficacy, different safety profiles for DCIS
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SAN ANTONIO — Postmenopausal women with ductal carcinoma in situ experienced comparable rates of recurrence but different adverse events when they received tamoxifen or anastrozole, according to results of the phase 3 IBIS-II DCIS study presented at the San Antonio Breast Cancer Symposium.
Rates of second gynecologic and non-melanoma cancers appeared higher among women who received tamoxifen, whereas cardiovascular events and fractures were higher in the anastrozole arm, according to study results, which were simultaneously published in The Lancet.
“We know that the third-generation aromatase inhibitors are more effective than tamoxifen for treating women with invasive breast cancer, but there is really limited, in fact very little data, for ductal carcinoma in situ [DCIS],” Jack Cuzick, PhD, professor and director of Wolfson Institute of Preventive Medicine at Queen Mary University of London, said during a press conference.
Data from the NSABP B-35 trial — presented at the 2015 ASCO Annual Meeting and also published in The Lancet — showed anastrozole (Arimidex, AstraZeneca) significantly reduced the risk for invasive and DCIS recurrence compared with tamoxifen among postmenopausal women with DCIS (HR = 0.73; P = .03).
Cuzick and colleagues of the IBIS-II study evaluated data from 2,980 postmenopausal women with locally excised hormone receptor-positive DCIS. The primary analysis included 1,449 women assigned 1 mg daily anastrozole and 1,489 women assigned 20 mg daily tamoxifen for 5 years.
All breast cancer recurrence served as the study’s primary endpoint.
Median follow-up was 7.2 years (interquartile range, 5.6-8.9).
Breast cancer recurrence — which included DCIS and invasive disease — occurred in 67 patients (6.6%) on the anastrozole arm and 77 (7.4%) on the tamoxifen arm (HR = 0.89; 95% CI, 0.64-1.23).
“There was a slightly better effect for anastrozole, with 11% fewer recurrences overall, but this was not statistically significant,” Cuzick said.
Anastrozole conferred a non-significant 20% reduction in invasive recurrences (37 vs. 47; HR = 0.8; 95% CI, 0.52-1.25); however, the rates of DCIS recurrence appeared comparable between the arms (29 vs. 30; HR = 0.99; 95% CI, 0.6-1.65).
Subgroup analyses indicated anastrozole may benefit patients with HER-2–negative disease (HR = 0.48; 95% CI, 0.26-0.84), ER-positive disease (HR = 0.59; 95% CI, 0.34-1.01) and ER-positive/HER-2–negative disease (HR = 0.37; 95% CI, 0.18-0.75), although Cuzick noted these were post-hoc analyses.
When Cuzick and colleagues conducted a meta-analyses with the data from the IBIS-II and NSABP B-35 trials, anastrozole appeared to significantly reduced the risk for breast cancer recurrence (HR = 0.79; 95% CI, 0.64-0.97).
Although the incidence of all secondary cancers was comparable between the anastrozole and tamoxifen cohorts, the incidence of specific cancers significantly differed. Fewer patients assigned anastrozole experienced a secondary endometrial cancer (1 vs. 11; OR = 0.09; 95% CI, 0.002-0.64) ovarian cancer (0 vs. 5; OR = 0; 95% CI, 0-0.79) and non-melanoma skin cancer (8 vs. 19; OR = 0.43; 95% CI, 0.16-1.03).
“We do know that tamoxifen increases endometrial cancer by two- to threefold, and there is emerging evidence that the estrogenic properties of anastrozole actually reduce endometrial cancer,” Cuzick said. “Together, there really is a dramatic reduction in endometrial cancer.”
Colorectal cancer (10 vs. 5; OR = 2.06; 95% CI, 0.64-7.71), lung cancer (11 vs. 7; OR = 1.62; 95% CI, 0.57-4.94) and lymphoma/leukemia (8 vs. 5; OR = 1.65; 95% CI, 0.47-6.42) occurred in more patients assigned anastrozole, but these associations did not reach statistical significance.
The fracture rate was higher in the anastrozole arm (129 vs. 100; OR = 1.36; 95% CI, 1.03-1.8), whereas major thromboembolic events were more common in the tamoxifen arm (24 vs. 7; OR = 0.3; 95% CI, 0.11-0.71). However, these were expected findings, Cuzick said.
A few more cardiovascular events occurred overall in the anastrozole arm (93 vs. 84; OR = 1.15; 95% CI, 0.84-1.57), but, when looking at individual events, there were significantly more cerebrovascular accidents (13 vs. 4; OR = 3.36; 95% CI, 1.04-14.18) and transient ischemic attacks (13 vs. 5; OR = 2.69; 95% CI, 0.9-9.65) in patients assigned anastrozole.
“This has not been seen previously, and we don’t really have a good explanation for it,” Cuzick said. “It’s something that needs to be looked at further.”
Any musculoskeletal adverse event occurred in more patients assigned anastrozole (64.1% vs. 54.5%; OR = 1.49; 95% CI, 1.28-1.74), whereas fewer vasomotor/gynecological events occurred in that cohort (60.7% vs. 69.2%; OR = 0.69; 95% CI, 0.59-0.8).
Overall, 5-year adherence rates were comparable in both arms (67.6% vs. 67.4%).
“We feel that anastrozole is now another agent that could be considered for ER-positive DCIS,” Cuzick said. “This offers another choice for women.” – by Alexandra Todak
References:
Cuzick J, et al. Abstract S6-03. Presented at: San Antonio Breast Cancer Symposium; Dec. 8-12, 2015; San Antonio.
Forbes JF, et al. Lancet. 2015;doi:10.1016/S0140-6736(15)01129-0.
Ganz PA, et al. Lancet. 2015;doi:10.1016/S0140-6736(15)01169-1.
Disclosure: Cuzick and one other researcher report research grants from AstraZeneca. Another researcher reports travel grants from Roche. The other researchers report no relevant financial disclosures.
Perspective
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C. Kent Osborne, MD
How to choose between these two therapies is a complicated issue. Does the patient already have osteoporosis? Do they have a history of thromboembolic phenomenon? If you put them on an aromatase inhibitor and they have intolerable joint pain, you can switch them. It’s just another option. Most patients prefer to be on tamoxifen — they just feel better on tamoxifen. Tamoxifen is probably going to remain the major therapy for this indication, with some exceptions.
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