Overweight, Obese Patients with Breast Cancer May Benefit Less from Docetaxel Treatment

A retrospective analysis of the adjuvant BIG 2-98 trial, which compared chemotherapy containing docetaxel to non-docetaxel-containing chemotherapy, found that patients with breast cancer who are overweight or obese may benefit less from treatment with docetaxel.¹

Researchers suggested that these results, published in the Journal of Clinical Oncology, still need to be confirmed in additional series. However, if confirmed, the investigators recommended a body composition-based reevaluation of the risk-benefit ratio of the use of taxanes in breast cancer be considered.

“If follow-up research confirms that this finding is solely related to the pharmacological characteristics of docetaxel, this might also apply to patients with other cancer types that are treated with docetaxel, such as prostate or lung cancer,” Christine Desmedt, PhD, of the KU Leuven Laboratory for Translational Breast Cancer Research, said in a press release.² “These results also make us wonder whether other chemotherapy drugs from the same family, like paclitaxel, will show the same effect.”

Overall, 2887 participants in the BIG 2-98 trial were retrospectively evaluated. Body mass index (BMI) was calculated using the height and weight measurements collected at the time of enrollment and categorized according to the WHO definitions of underweight (< 18.5 kg/m2), lean (≥ 18.5 and < 25 kg/m2), overweight (≥ 25 and < 30 kg/m2), and obese (≥ 30 kg/m2).

The primary end point of the study was disease-free survival (DFS) and the secondary end point was overall survival (OS).

No difference was observed in DFS or OS according to BMI in the non-docetaxel group, whereas reduced DFS and OS were associated with increasing BMI in the docetaxel group. Adjusted hazard ratios for DFS and OS were 1.12 (95% CI, 0.98-1.50; P = .21) and 1.27 (95% CI, 1.01-1.60; P = .04) for overweight versus lean groups, respectively, and 1.32 (95% CI, 1.08-1.62; P = .007) and 1.63 (95% CI, 1.27-2.09; P = .001) for obese versus lean groups, respectively.

Similar results were seen when estrogen receptor (ER)-negative and ER+ tumors were considered separately and when considering only patients who received a relative dose intensity of 85% or less for docetaxel. Moreover, a joint modifying role of BMI and ER status on treatment effect was apparent for DFS (adjusted P = .06) and OS (adjusted P = .04).

“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,” the authors noted.

The investigators indicated that the considered trial is unique, as no other trial has compared the efficacy of taxane-based versus non-taxane-based regimens in the adjuvant setting without an upfront capping of the body surface area in heavier patients to calculate the chemotherapeutic doses to be administered. Moving forward, the researchers are currently developing a prospective pharmacokinetics study and will be performing similar analyses in other adjuvant trials evaluating taxanes for treating breast cancer.

“More research is needed before changes in treatment can be implemented. Patients who have concerns about docetaxel can discuss these with their doctor,” Desmedt explained in the release. “In general, the public needs to be better informed about the link between BMI and breast cancer.”

References:

1. Desmedt C, Fornili M, Clatot F, et al. Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index. Journal of Clinical Oncology. doi: 10.1200/JCO.19.01771.

2. Popular chemotherapy drug may be less effective in overweight and obese women [news release]. Published July 3, 2020. nieuws.kuleuven.be/en/content/2020/popular-chemotherapy-drug-may-be-less-effective-in-overweight-and-obese-women. Accessed August 4, 2020.