According to results from a prospective, open-label, phase III study conducted in 69 Italian hospitals within the Gruppo Italiano Mammella among the postmenopausal patients with stage I to III breast cancer who were treated with 2 to 3 years of tamoxifen, extended treatment with 5 years of letrozole resulted in longer disease-free survival (DFS) and overall survival (OS) compared to the treatment with 2 to 3 years of letrozole. The results were presented by Prof. Lucia del Mastro of the Breast Unit, Università degli Studi di Genova, Ospedale Policlinico San Martino in Genova, Italy in a proffered papers session on early stage breast cancer during the ESMO Congress 2021 (16-21 September).
Prof. del Mastro explained that benefit of extended adjuvant treatment with aromatase inhibitors in postmenopausal patients with hormone receptor (HR)-positive breast cancer treated with tamoxifen for 2 to 3 years and followed by an aromatase inhibitor for 2 to 3 years is still controversial. Breast cancer researchers from 64 Italian hospitals aimed within the Gruppo Italiano Mammella to determine whether, after 2 to 3 years of treatment with tamoxifen, 5 years of letrozole is more effective than the standard duration of letrozole treatment of 2 to 3 years.
They randomised (1:1) patients with stage I to III breast cancer who were free of recurrence after 2 to 3 years of tamoxifen, to receive 2 to 3 years (control arm) or 5 years (extended arm) of letrozole. Primary endpoint was DFS in the intention-to-treat population. The OS and safety were secondary endpoints.
Between 1 August 2005 and 24 October 2010, the study team recruited 2056 patients. After a median follow-up of 11.7 years (IQR 9.5-13.1), 262 of 1030 patients (25%) in the control arm and 212 of 1026 patients (21%) in the extended arm experienced a DFS event. The 12-year DFS was 62% (95% confidence interval [CI] 57-66) in the control arm and 67% (95% CI 62-71) in the extended arm (hazard ratio [HR] 0.78, 0.65-0.93; p = 0.006).
The effect did not change in a multivariate Cox model including nodal status, tumour size, grading, age, HR status, HER2 status, previous chemotherapy, and BMI (p = 0·014).
In total, 263 deaths (13%) occurred, 147 in the control arm and 116 in the extended arm. The 12-year OS was 84% (95% CI 82-87) in the control arm and 88% (95% CI 86-90) in the extended arm (HR 0.77, 0.60-0.98; p = 0.036).
In terms of side effects, arthralgia (31% vs 38%), myalgia (8% vs 12%), hypertension (1% vs 2%) and osteoporosis (5% vs 8%) were significantly more frequent in the extended arm.
The authors concluded that extended adjuvant treatment with 5 years of letrozole resulted in a significant and clinically meaningful improvement in DFS and OS.
The study results were simultaneously published in The Lancet Oncology.
Dr. Monica Arnedos of the Breast Unit, Institut Bergonié in Bordeaux, France who discussed the implications of the study results said that the study adds additional evidence to support extended treatment with aromatase inhibitor in postmenopausal patients, notably after 2-3 years of adjuvant tamoxifen even in clinically low-risk patients for a total duration of 7 to 8 years of endocrine treatment. However, long-term follow-up data from this study is awaiting and it is needed to better define population benefiting from extended treatment.
The study was funded by Novartis and Italian Ministry of Health.
- 118O – 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 randomised, phase III trial of the Gruppo Italiano Mammella. ESMO Congress 2021 (16-21 September).
- 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. The Lancet Oncology; Published online 17 September 2021. DOI: https://doi.org/10.1016/S1470-2045(21)00352-1