Extended letrozole therapy improves DFS in postmenopausal women with breast cancer

Extending treatment with letrozole for 5 years improves disease-free survival (DFS) rates in postmenopausal women with early-stage breast cancer who have already received tamoxifen for 2–3 years, according to the GIM4* trial.

This phase III, multicentre, open-label trial involved 2,056 patients with stage I–III histologically proven and operable invasive hormone receptor-positive breast cancer who were recruited from 69 hospitals in Italy. Participants were randomized in a 1:1 ratio to receive oral letrozole 2.5 mg once daily for 2–3 years (control group; n=1,030, mean age 60 years) or 5 years (extended group; n=1,026, mean age 61 years) after 2–3 years of tamoxifen therapy. [Lancet Oncol 2021;22:1458-1467]

Overall, 212 and 262 DFS events occurred in the extended and the control group, respectively.

The 12-year DFS rate was higher among patients treated with letrozole for 5 years compared with a shorter course of 2–3 years (67.0 percent vs 62.0 percent; hazard ratio [HR], 0.78, 95 percent confidence interval [CI], 0.65–0.93; p=0.0064) at a median follow-up of 11.7 years.

Patients treated with letrozole for 5 years also achieved a higher 12-year overall survival (OS) rate than those on letrozole for 2–3 years (88.0 percent vs 84.0 percent; HR, 0.77, 95 percent CI, 0.66–0.98; p=0.036). “To our knowledge, GIM4 is the clinical trial of extended aromatase inhibitor [letrozole] therapy with the longest follow-up and the first study showing an OS benefit by extending aromatase inhibitor treatment beyond 5 years,” the researchers noted.

However, grade 3–4 arthralgia (3.0 percent vs 2.2 percent) and myalgia (0.9 percent vs 0.7 percent) occurred at a higher rate in the extended group than the control group, with eight and three treatment-related serious AEs reported, respectively.

No cases of deaths related to toxic effects were reported.

“[Overall, results showed that] in postmenopausal patients with hormone receptor-positive breast cancer who received adjuvant tamoxifen for 2–3 years, extended therapy with 5 years of letrozole significantly improved DFS and OS outcomes compared with the standard 2–3 years of letrozole,” the researchers concluded.

“Considering all available evidence, … sequential endocrine therapy with tamoxifen for 2–3 years followed by [the use of] letrozole for 5 years should be considered as one of the optimal standard endocrine treatments for postmenopausal patients with hormone receptor-positive breast cancer,” they added.

*GIM4: Letrozole in treating breast cancer in postmenopausal women with stage I, II, or III breast cancer previously treated with tamoxifen