An Italian phase III trial (FATA-GIM3) has shown no difference in disease-free survival with 5 years of upfront adjuvant aromatase inhibitor therapy vs 2 years of tamoxifen followed by 3 years of aromatase inhibitor therapy in women with hormone receptor–positive early breast cancer. The findings were reported in The Lancet Oncology by De Placido et al.
In the open-label trial, 3,697 patients were randomized between March 2007 and July 2012 to one of six treatment groups: oral anastrozole (1 mg/d), exemestane (25 mg/d), or letrozole (2.5 mg/d) for 5 years (upfront strategy) or oral tamoxifen (20 mg/d) for 2 years followed by one of the three aromatase inhibitors for 3 years (switch strategy).
The primary endpoint was disease-free survival, with the minimum cutoff to declare superiority of the upfront strategy over the switch strategy considered to be a 2% difference in disease-free survival at 5 years. Follow-up in the trial is ongoing.
After median follow-up of 60 months, disease-free survival events had occurred in 211 (11%) of 1,850 patients receiving the switch strategy and 190 (10%) of 1,847 receiving upfront treatment. Disease-free survival at 5 years was 88.5% with the switch strategy vs 89.8% with upfront treatment (hazard ratio = 0.89, P = .23). Overall, 5-year disease-free survival was 90.0% with anastrozole, 88.0% with exemestane, and 89.4% with letrozole (P = .24).
Musculoskeletal adverse events were the most frequent grade 3 or 4 events, occurring in 7% of 1761 patients with the switch strategy and 7% of patients with upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront strategy (52% vs 42%). All other grade 3 or 4 adverse events occurred in < 2% of both the switch and upfront groups. No unexpected serious adverse events or treatment-related deaths were observed.
The investigators concluded, “5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting.”
The study was funded by the Italian Drug Agency.
Francesco Perrone, MD, of Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione Pascale, IRCCS, Naples, is the corresponding author for The Lancet Oncology article.
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