Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial
Mené en Italie sur 2 056 patientes atteintes d'un cancer du sein de stade précoce après la ménopause, cet essai de phase III compare l'efficacité, du point de vue de la survie sans maladie invasive, et la toxicité de deux durées de traitement adjuvant à base de létrozole (durée standard de 2-3 ans et durée étendue à 5 ans)
Background : The benefit of extending aromatase inhibitor therapy beyond 5 years in the contextof previous aromatase inhibitors remains controversial. We aimed to compare extended therapy with letrozole for 5 years versus the standard duration of 2–3 years of letrozole in postmenopausal patients with breast cancer who have already received 2–3 yearsof tamoxifen. Methods : This multicentre, open-label, randomised, phase 3 trial was done at 69 hospitals in Italy. Women were eligible if they were postmenopausal at the time of study entry,had stage I–III histologically proven and operable invasive hormone receptor-positivebreast cancer, had received adjuvant tamoxifen therapy for at least 2 years but nolonger than 3 years and 3 months, had no signs of disease recurrence, and had an EasternCooperative Oncology Group performance status of 2 or lower. Patients were randomlyassigned (1:1) to receive 2–3 years (control group) or 5 years (extended group) ofletrozole (2·5 mg orally once a day). Randomisation, with stratification by centre,with permuted blocks of size 12, was done with a centralised, interactive, internet-basedsystem that randomly generated the treatment allocation. Participants and investigatorswere not masked to treatment assignment. The primary endpoint was invasive disease-free survival in the intention-to-treat population. Safety analysis was done for patientswho received at least 1 month of study treatment. This trial was registered with EudraCT,2005-001212-44, and ClinicalTrials.gov, NCT01064635. Findings : Between Aug 1, 2005, and Oct 24, 2010, 2056 patients were enrolled and randomly assignedto receive letrozole for 2–3 years (n=1030; control group) or for 5 years (n=1026;extended group). After a median follow-up of 11·7 years (IQR 9·5–13·1), disease-freesurvival events occurred in 262 (25·4%) of 1030 patients in the control group and212 (20·7%) of 1026 in the extended group. 12-year disease-free survival was 62% (95%CI 57–66) in the control group and 67% (62–71) in the extended group (hazard ratio0·78, 95% CI 0·65–0·93; p=0·0064). The most common grade 3 and 4 adverse events werearthralgia (22 [2·2%] of 983 patients in the control group vs 29 [3·0%] of 977 in the extended group) and myalgia (seven [0·7%] vs nine [0·9%]). There were three (0·3%) serious treatment-related adverse events inthe control group and eight (0·8%) in the extended group. No deaths related to toxiceffects were observed. Interpretation : In postmenopausal patients with breast cancer who received 2–3 years of tamoxifen,extended treatment with 5 years of letrozole resulted in a significant improvementin disease-free survival compared with the standard 2–3 years of letrozole. Sequentialendocrine therapy with tamoxifen for 2–3 years followed by letrozole for 5 years shouldbe considered as one of the optimal standard endocrine treatments for postmenopausalpatients with hormone receptor-positive breast cancer.
The Lancet Oncology 2021