No Association Between Taxane-Induced Neuropathy and Clinical Outcomes in Early Breast Cancer

According to an analysis of the Eastern Cooperative Oncology Group trial ECOG-E1199 by Schneider and colleagues, the development of grade 2 to 4 peripheral neuropathy in patients with operable breast cancer who received taxanes does not appear to affect clinical outcome.¹

“We found that, although neuropathy was a common complication that was associated with necessary dose reductions [of taxanes], it was not associated with a higher risk of recurrence or inferior survival,” wrote Bryan P. Schneider, MD, and colleagues. Schneider is affiliated with ECOG at the Indiana University School of Medicine, Indianapolis.

The investigators of this study previously identified several single nucleotide polymorphisms that were significantly associated with an increased risk for developing grade 2 to 4 peripheral neuropathy in patients with breast cancer treated with taxane-containing chemotherapy. The present study suggests that this biomarker will not be useful for identifying patients who will derive preferential benefit from taxane therapy.

“This finding provides reassurance that biomarkers predictive for neuropathy will likely not enrich for patients who are more likely to benefit from taxane therapy and may also be useful for the identification of patients who are most likely to benefit from adjunctive therapies to mitigate neuropathy,” wrote the authors.

The study population included 4554 women with operable breast cancer—either axillary node-positive or high-risk node-negative breast cancer. They were treated with up to 4 cycles of doxorubicin/cyclophosphamide every 3 weeks and then randomized to 1 of 4 treatment arms: 4 cycles of paclitaxel 175 mg/m² every 3 weeks (arm P3), 12 cycles of paclitaxel 80 mg/m2 every week (arm P1), 4 cycles of docetaxel 100 mg/m² every 3 weeks (arm D3), or 12 cycles of docetaxel 35 mg/m2 every week (arm D1). Grade 2 to 4 peripheral neuropathy was evaluated using the National Can­cer Institute Common Toxicity Criteria (version 2.0) grading scale. End points were overall survival, disease-free survival, and recurrence-free survival.

Grade 2 to 4 neuropathy developed in 18%, 22%, 15%, and 13% of patients in the P3, P1, D3, and D1 treatment arms, respectively. In a model adjusted for age, race, obesity, menopausal status, tumor size, nodal status, treatment arm, neuropathy, and hypergly­cemia, no significant relationship was observed between neuropathy and the 3 end points.

The risk of neuropathy was decreased in premenopausal patients compared with postmenopausal patients, and the risk of neuropathy was higher in blacks than in other races and in obese patients versus nonobese patients. The association between hyperglycemia and neuropathy was significant and remained significant after adjusting for age, race, obesity, and menopausal status. Hy­pe­r­glycemia was also associated with inferior outcomes, but only in the P3 arm.

“These findings must…be interpreted with caution because treatment-associated hyperglycemia may be multifactorial and not reflect patients with a formal diagnosis of diabetes,” the authors wrote.

Reference

1. Schneider BP, Zhao F, Wang M, et al. Neuropathy is not associated with clinical outcomes in patients receiving adjuvant taxane-containing therapy for operable breast cancer. J Clin Oncol. 2012;30:3051-3057.