medwireNews: The efficacy of aromatase inhibition is comparable regardless of whether the agents are taken upfront for 5 years or for 3 years following 2 years of tamoxifen in postmenopausal women with hormone receptor-positive, early-stage breast cancer, researchers report.
The phase III FATA-GIM3 trial also showed that there was no significant difference in disease-free survival between each of the three aromatase inhibitors tested, namely anastrozole, exemestane, and letrozole.
“Therefore, patient preference, tolerability, and financial constraints should be considered when choosing which schedule and which aromatase inhibitor to include in the therapeutic plan for adjuvant hormonal treatment of postmenopausal patients with early breast cancer,” Francesco Perrone (Fondazione Pascale IRCCS, Naples, Italy) and co-authors write in The Lancet Oncology.
Perrone and team randomly assigned half of the women in the trial (n=1847) to receive upfront treatment with oral anastrozole (1 mg/day), exemestane (25 mg/day), or letrozole (2.5 mg/day) for 5 years.
The other half (n=1850) were randomly assigned to follow a switch strategy in which they received oral tamoxifen (20 mg/day) for 2 years followed by one of the three aromatase inhibitors, at the same dosage as the upfront strategy, for 3 years.
All patients had invasive hormone receptor-positive breast cancer that had been completely removed by surgery.
The researchers report that there was no significant difference in 5-year disease-free survival (DFS) between the two treatment strategies, at 89.8% with upfront treatment versus 88.5% with the switch strategy. There was also no difference in 5-year overall survival (OS) between the two groups, at 96.8% and 95.3%, respectively.
Furthermore, 5-year DFS between did not differ significantly among each of the aromatase inhibitors used, at 90.0%, 88.0%, and 89.4% for anastrozole, exemestane, and letrozole, respectively. The corresponding 5-year OS rates were a comparable 95.9%, 95.7% and 96.6%.
The most commonly reported side effects were musculoskeletal in nature; the overall rate of musculoskeletal adverse events was significantly higher in the upfront group than in the switch group, owing to a higher rate of grade 1 events (52 vs 42%). The rate of grade 3–4 musculoskeletal events, however, was 7% in each group.
The majority of side effects did not differ between each of the aromatase inhibitors used, but gastrointestinal events were more common with exemestane than with letrozole, while hypercholesterolemia was more common with anastrozole and letrozole than with exemestane.
In an accompanying commentary, Luc Dirix, from the University of Antwerp in Belgium, describes FATA-GIM3 as an “important confirmatory study” that allows medical professionals and their patients to be “confident that any aromatase inhibitor is acceptable in this treatment strategy.”
He adds: “Toxicity, safety profile, and costs do clearly differ between these two schedules, so the reassuring absence of a substantial clinical difference in outcome leaves room for treatment selection based on pre-existing medical conditions, patient preferences, and financial constraints.”
And Dirix concludes that “even if the upfront strategy is preferred, FATA-GIM3 confirms the absence of a relevant difference between the aromatase inhibitors (with only small differences in toxicities but not in efficacy), giving clinicians the freedom to exchange one aromatase inhibitor for another.”
By Laura Cowen
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