We all know postmenopausal patients with early stage hormone receptor positive breast cancer benefit from adjuvant treatment with aromatase inhibitors but two main questions were left open by randomized trials the OPTIMAL schedule and whether the three aromatases inhibitors are interchangeable this is an assumption that is widely applied in clinical practice but was never tested so gene 3 fata is a fully academic investigator initiated and the only randomized trial that allocated patients to all three third generation aromatase inhibitors and to both schedules within one protocol in the first report of the gym 3 fata in published in lancet 2018 we found no difference in terms of disease free survival or overall survival either with the schedule or between the three aromatases inhibitors, and now we present the final analysis the study Looking at the study design the trial enrolled early stage postmenopausal patients with hormone receptor positive breast cancer after surgery and after adjuvant or neoadjuvant therapy the patients were assigned in a two times three factorial design to one of the six treatment arms and the study was powered to detect a two percent absolute difference in five-year disease-free survival between the switch and the upfront schedule according to the factorial design the study was also powered to detect a 2 % absolute difference in five-year disease-free survival between the three aromatase inhibitors independently from the schedule...
We all know postmenopausal patients with early stage hormone receptor positive breast cancer benefit from adjuvant treatment with aromatase inhibitors but two main questions were left open by randomized trials the OPTIMAL schedule and whether the three aromatases inhibitors are interchangeable this is an assumption that is widely applied in clinical practice but was never tested so gene 3 fata is a fully academic investigator initiated and the only randomized trial that allocated patients to all three third generation aromatase inhibitors and to both schedules within one protocol in the first report of the gym 3 fata in published in lancet 2018 we found no difference in terms of disease free survival or overall survival either with the schedule or between the three aromatases inhibitors, and now we present the final analysis the study Looking at the study design the trial enrolled early stage postmenopausal patients with hormone receptor positive breast cancer after surgery and after adjuvant or neoadjuvant therapy the patients were assigned in a two times three factorial design to one of the six treatment arms and the study was powered to detect a two percent absolute difference in five-year disease-free survival between the switch and the upfront schedule according to the factorial design the study was also powered to detect a 2 % absolute difference in five-year disease-free survival between the three aromatase inhibitors independently from the schedule. If the global three-way comparison was statistically significant, pre-specified per-virus comparisons were performed. The primary endpoint of the study was the disease – free survival. Key secondary endpoints were overall survival and safety. Going to the results, the study cohort enrolled nearly 3 ,700 patients and baseline characteristics were well-balanced among treatment harms. After a median follow-up of 88 .9 months, we found no difference in terms of disease-free survival or overall survival in the switch versus upfront comparison at 10 years. In the 10-year head-to-head comparison between the three aromatase inhibitors, disease – free survival was significantly worse with a stem enzyme than with an astrazole, with a 4 .9 % delta at 10 years, favoring the anastrozole and no difference in terms of overall survival. Talking about the safety, well, we found no new safety signals in our study besides the well-known drug-specific effects. High cholesterol was more frequent in the upfront arm and were treated either with anastrazole or letrozole. Bone fracture rates were similar across the aromatase inhibitors. The main limitations are that late recurrences continue to accrue in hormone-receptor-positive disease even beyond 10 years and that the extended endocrine therapy was not a standard at the time of the trial. So, in this study, we didn’t collect any on blood samples in the patients. So, we don’t have specific data on blood circulating biomarkers. Whatever we can say, it’s coming from the subgroup analysis that we ran in the study. And so, in all subgroup analyses, what we see is that the difference between anastrozole and dexamethasone is directionally consistent across all sub-groups. And it’s particularly evident when we talk about low risk patients in two specific, in non-negative patients and in patients treated with no prior chemotherapy. So, the difference that we see in the study regarding the bone health into specific is particularly evident when you look at the comparison between the upfront arm and the switch schedule. And this is because in the switch schedule, the patients started with two years of tamoxifen. And from the mechanism of action of the tamoxifen, we know very well that the tamo is protective with regard to the bone. And so, those patients did a little bit better with the osteoporosis and the bone fractures. When starting with the aromatase inhibitors, we all know that it’s very important to treat the patients either with biphosphonates or denosumab. And actually now, the drugs that we have, like for example, at the time of the trial, the denosumab was not a standard. Now, treating patients with denosomab, we have a very effective drug in managing the osteoporosis. And it can be widely used in the patients, and it’s very manageable and safe for patients at the dosage of early stage breast cancer patients.
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