Optimal duration of extended adjuvant endocrine therapy for early breast cancer; results of the IDEAL trial (BOOG 2006-05)

Background: The optimal duration of extended endocrine therapy beyond five years after initial aromatase inhibitor-based adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer is still unknown. Therefore, we conducted a clinical trial to compare two different extended endocrine therapy durations. Methods: In the randomized phase III IDEAL trial, postmenopausal patients with hormone receptor-positive breast cancer were randomly allocated to either 2.5 or five years of letrozole after the initial five years of any endocrine therapy. The primary end point was disease free survival (DFS), and secondary end points were overall survival (OS), distant metastasis-free interval (DMFi), new primary breast cancer, and safety. Hazard ratios (HRs) were determined using Cox regression analysis. All analyses were by intention-to-treat principle. Results: A total of 1824 patients were assigned to either 2.5 years (n ¼ 909) or five years (n ¼ 915) of letrozole, with a median follow-up of 6.6 years. A DFS event occurred in 152 patients in the five-year group, compared with 163 patients in the 2.5-year group (HR ¼ 0.92, 95% confidence interval [CI] ¼ 0.74 to 1.16). OS (HR ¼ 1.04, 95% CI ¼ 0.78 to 1.38) and DMFi (HR ¼ 1.06, 95% CI ¼ 0.78 to 1.45) were not different between both groups. A reduction in occurrence of second primary breast cancer was observed with five years of treatment (HR ¼ 0.39, 95% CI ¼ 0.19 to 0.81). Subgroup analysis did not identify patients who benefit from five-year extended therapy. Conclusion: This study showed no superiority of five years over 2.5 years of extended adjuvant letrozole after an initial five years of adjuvant endocrine therapy.