medwireNews: Women with early-stage breast cancer have a differential response to adjuvant docetaxel therapy according to their BMI, finds a post-hoc analysis of a phase 3 trial.
Disease-free survival (DFS) and overall survival (OS) were significantly poorer in docetaxel-treated participants who were overweight and obese than in their normal-weight counterparts, but such an association was not observed among those who did not receive docetaxel, report Christine Desmedt, from KU Leuven in Belgium, and fellow investigators.
They therefore write in the Journal of Clinical Oncology: “If the results are confirmed in additional series, then a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes should be considered.”
The team analyzed data from the 1346 normal-weight (BMI ≥18.5 and <25 kg/m2), 951 overweight (≥25 and <30 kg/m2), and 542 obese (≥30 kg/m2) participants of the BIG 2-98 trial that investigated the sequential or concurrent addition of docetaxel to adjuvant doxorubicin, cyclophosphamide, methotrexate, and fluorouracil for clinical stage T1–T3 disease with at least one positive lymph node.
The impact of BMI on DFS in docetaxel-treated patients persisted after adjusting for age, tumor size, nodal status, and estrogen receptor (ER) status, with hazard ratios (HRs) of 1.12 and 1.32 for overweight and obese patients, respectively, versus normal-weight patients, albeit without statistical significance for the overweight group.
The results were similar for OS, with significant HRs of 1.27 and 1.63 when overweight and obese participants, respectively, were compared with their normal-weight counterparts.
“The present observations could be explained by the lipophilic nature of docetaxel, which results in a higher volume of distribution and a decreased efficacy at the distant level in patients with increased BMI,” write the study authors.
And they continue: “[I]f the pharmacologic properties of docetaxel are indeed causing the observed differences in treatment efficacy according to patient adiposity, we could expect similar results for paclitaxel, another lipophilic drug from the taxane family widely used for the treatment of [breast cancer].”
Desmedt and colleagues also found evidence for “a joint modifying role of BMI and ER status on the treatment effect.” In the ER-negative subgroup, DFS and OS were significantly worse for both overweight and obese participants relative to normal-weight participants, while outcomes were poorer only for obese patients in the ER-positive subgroup.
Therefore, the benefit of docetaxel-based treatment “could be limited to lean and overweight patients with ER-positive tumors and, possibly, to lean patients with ER-negative tumors,” the researchers summarize, but they add that the results “should be taken with caution, given the multiplicity of the tests.”
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