Patients who were given extended 5-year treatment with letrozole plus 2 to 3 years of tamoxifen experienced an improvement in disease-free survival compared with 2 to 3 years of treatment with letrozole.
Patients who received extended treatment with letrozole for 5 years following 2 to 3 years of treatment with tamoxifen (Nolvadex) experienced an improved disease-free survival (DFS) over 2 to 3 years of letrozole for patients with postmenopausal hormone receptor–positive breast cancer, according to findings from the phase 3 LEAD study (NCT01064635) that were published in The Lancet Oncology.
After a median follow-up of 11.7 years, investigators reported a DFS rate of 25.4% among patients in the control group, and 20.7% in the extended group. The 12-year DFS was 62% (95% CI, 57%-66%) in the control group compared with 67% (95% CI, 62%-71%) in the extended treatment group (HR, 0.78; 95% CI, 0.65-0.93; P = .0064).
A total of 2056 patients were enrolled on the study and randomized to receive 2.5 mg of letrozole for either 2 to 3 years (n = 1030), or 5 years (n = 1026) plus tamoxifen. The median patient age was 61 years, and 12.2% of patients who were HER2-positive received treatment with trastuzumab (Herceptin).
Letrozole was discontinued in 19.5% of patients in the control group and 37.1% in the extended group. In the first 2 to 3 years of randomization, 23.0% discontinued letrozole and 14.0% discontinued in the following years. Reasons for discontinuation in both the control and extended treatment cohorts, respectively, included adverse effects (AEs; 8.9 vs 14.4%) and refusal of treatment (3.8% vs 10.4%).
During the study, 12.8% of patients died, including 147 patients in the control group, and 116 in the extended treatment group. The 12-year overall survival in the control group was 84% (95% CI, 82%-87%) compared with 88% (95% CI, 86%-90%) in the extended group (HR, 0.77; 95% CI, 0.60-0.98; P = .036).
A post-hoc landmark analysis was conducted that included 1890 patients, excluding patients with a disease-free survival event or those lost to follow-up. The 10-year disease-free survival after treatment divergence was 59% (95% CI, 53%-64%) in the control group and 68% (95% CI, 63%-72%) in the extended group (HR, 0.73; 95% CI, 0.60-0.90; P = .0022).
The most common AEs that led to discontinuation in both the control group and extended treatment group, respectively, were arthralgia (4.3% vs 7.7%) and myalgia (<1% vs <1%). Patients had a median duration of treatment with letrozole of 2.4 years in the control group and 5.0 years in the extended group.
In terms of safety, the most common grade 3/4 AEs in the control and extended treatment cohorts, respectively, were arthralgia (2.2% vs 3.0%) and myalgia (0.7% vs 0.9%). Other AEs included osteoporosis (4.7% vs 8.3%), hypercholesterolemia (3.1% vs 2.0%; P = .17), and cardiovascular events (0.1% vs 0.6%; P = .069).
Additionally, 0.3% of patients in the control group experienced treatment-related serious AEs such as atrial fibrillation, bone pain, and vomiting, compared with 0.8% in the extended treatment group who experienced pneumonia, macular degeneration, thromboembolic, and cardiovascular events. No deaths occurred as a result of 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