Extended treatment with letrozole significantly improved survival in postmenopausal patients with early-stage breast cancer, according to results of a phase 3 trial published in The Lancet Oncology.

When compared with the standard 2-3 years of letrozole, 5 years of letrozole treatment improved both disease-free survival (DFS) and overall survival (OS).

Researchers compared the 2 treatment durations in the phase 3 GIM4 trial (ClinicalTrials.gov Identifier: NCT01064635). The trial enrolled 2056 patients with hormone receptor-positive breast cancer who had received adjuvant tamoxifen for at least 2 years but no longer than 3 years and 3 months.


Continue Reading

The patients were randomly assigned to receive letrozole at 2.5 mg daily for 2-3 years (control arm; 1030 patients) or 5 years (extended arm; 1026 patients).

At baseline, the patients’ median age was 61 years (range, 54-68 years). About three-quarters of patients in each arm had breast-conserving surgery, more than half had no regional lymph node metastasis, and more than 80% had estrogen and progesterone receptor-positive disease.

The median duration of letrozole treatment was 2.4 years in the control arm and 5.0 years in the extended arm.

At a median follow-up of 11.7 years, DFS events occurred in 20.7% of patients in the extended arm and 25.4% of patients in the control arm.  

In the intent-to-treat population, the 12-year DFS rate was significantly higher in the extended arm than in the control arm — 67% and 62%, respectively (hazard ratio [HR], 0.78; 95% CI, 0.65-0.93; P =.0064). The improvement in DFS persisted in a multivariate analysis (HR, 0.79; 95% CI, 0.66-0.95; P =.014).

A total of 263 deaths (12.8%) were reported, 116 in the extended arm and 147 in the control arm.

The 12-year OS rate was significantly higher in the extended arm than in the control arm — 88% and 84%, respectively (HR, 0.77; 95% CI, 0.60-0.98; P =.036).

As for adverse events (AEs), osteoporosis was more common in the extended arm than in the control arm — 8.3% and 4.7%, respectively. The extended and control arms had similar rates of bone fracture (0.9% and 0.5%), hypercholesterolemia (2.0% and 3.1%), and cardiovascular events (0.6% and 0.1%).

The most common grade 3-4 AEs (in the extended and control arms, respectively) were arthralgia (3.0% and 2.2%) and myalgia (0.9% and 0.7%).

Serious treatment-related AEs were observed in 0.8% of patients in the extended arm and 0.3% in the control arm. There were no treatment-related fatalities.

“Sequential endocrine therapy with tamoxifen for 2-3 years followed by letrozole for 5 years should be considered as one of the optimal standard endocrine treatments for postmenopausal patients with hormone receptor-positive breast cancer,” the researchers concluded.

Disclosures: This research was supported by Novartis and the Italian Ministry of Health. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

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