Initial treatment with tamoxifen (Soltamox) and letrozole for 2 to 3 years plus 5 years of extended treatment with letrozole appears to increase disease-free survival (DFS) for patients with breast cancer who are postmenopausal, according to findings from a phase 3 study (NCT01064635) published in The Lancet Oncology.
At the median follow-up of 11.7 years, DFS events were observed in 262 of 1030 patients in the control group, and 212 of 1026 patients in the extended group. Investigators reported a 12-year DFS rate of 62% (95% CI, 57%-66%) compared with 67% (95% CI, 62%-71%) in the extended group (HR, 0.78; 95% CI, 0.65-0.93; P = .0064).
A total of 2056 patients enrolled on the trial and were randomly assigned to either the control group (n = 1030) or the extended group (n = 1026). The median patient age was 61, and 15 patients between both groups were HER2-positive and received adjuvant trastuzumab (Herceptin).
Patients received 2.5 mg orally of adjuvant letrozole once daily, after patients had received 2 to 3 years of tamoxifen; letrozole was administered for 2 to 3 years in the control group and for 5 years in the experimental group. Those in the control group received 5 years of adjuvant endocrine therapy compared with 7 to 8 years in the extended group. Additionally, dose reductions were not allowed.
Discontinuation of letrozole was seen in 189 patients in the control group, and 344 in the extended group. In total, 79 patients in the extended group discontinued letrozole 2 to 3 years after randomization, and 48 discontinued in subsequent years. Reasons for discontinuation included adverse effects (AEs) and patient refusal.
Patients had a median duration of treatment with letrozole was 2.4 years in the control group and 5.0 years in the extended group. In the control group, 147 patients died, and 116 died in the extended group. Moreover, the 12-year overall survival (OS) rate in the control group was 84% (95% CI, 82%-87%) and 88% (95% CI, 86%-90%) in the extended group (HR, 0.77; 95% CI, 0.60-0.98; P = .036).
The 5-year DFS rate in the post-hoc analysis was 92% (95% CI, 91%-94%) in the control group and 92% (95% CI, 90%-94%) in the extended group. The 10-year DFS rate was 74% (95% CI, 71%-77%) and 79% (95% CI, 75%-82%). Additionally, the 5-year OS rate was 97% (95% CI, 96%-98%) in the control group and 97% (95% CI, 95%-98%) in the extended group. The 10-year OS was 90% (5% CI, 88%-92%) and 91% (95% CI, 89%-93%) in both respective arms.
AEs that led to discontinuation in the control and letrozole groups, respectively, included arthralgia (4.3% vs 7.7%) and myalgia (<1% vs <1%). The most common grade 3/4 AEs were included arthralgia (2.2% vs 3.0%) and myalgia (0.7% vs 0.9%) in the control and extended groups, respectively. Patients also experienced osteoporosis (4.7% vs 8.3%), bone fractures (0.5% vs 0.9%), hypercholesterolemia (3.1% vs 2.0%), and cardiovascular events (0.1% vs 0.6%) in the control group and extended group, respectively.
Treatment-related serious AEs were observed in 3 patients in the control group, and included atrial fibrillation, bone pain, and vomiting. Eight patients in the extended group also experienced treatment-related serious AEs, including pneumonia, macular degeneration, thromboembolic, and cardiovascular events. No patient died from toxic effects.
Del Mastro L, Mansutti M, Bisagni G, et al. Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(10):1458-1467. doi:10.1016/S1470-2045(21)00352-1
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