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Top Line: The hard truth is that the majority of women in the US are overweight or obese.
The Study: Taxanes, which are widely used in breast cancer, are lipophilic drugs. So could differences in drug biodistribution result in different treatment outcomes? BIG 2-98 (so named without this add-on study in mind, we presume) was a 4-armed, RTOG 9413-esque randomized trial of doxorubicin + docetaxel versus doxorubicin +/- cyclophosphamide both followed by CMF for breast cancer. Here's a secondary analysis of survival outcomes based on BMI. Among patients receiving a docetaxel-containing regimen, those who were overweight and obese had inferior disease free (DFS) and overall survival (OS) as well as a higher rate of distant metastases. These differences were not observed between the lean and obese patients in the non-docetaxel study arms. In fact, BMI as a continuous variable was associated with worse survival outcomes among those receiving docetaxel. Why? Well, for one, heavier patients in the docetaxel arms were more likely to have reduced intensity of chemotherapy. However, survival outcomes remained inferior when that subset of patients was removed from the comparison. The hypothesis here is that highly lipophilic docetaxel gets distributed in peripheral fat resulting in reduced effect in patients with higher BMI, perhaps even more concerning for docetaxel’s lipophilic sister paclitaxel.
TBL: The efficacy of lipophilic docetaxel appears inferior in overweight and obese women with breast cancer. | Desmedt, J Clin Oncol 2020