A recent phase 2 study, ECOG-ACRIN EAZ171, presented at the 2024 ASCO Annual Meeting and published in the Journal of Clinical Oncology, indicates that docetaxel administered every three weeks may be a preferable taxane for Black women with early-stage breast cancer due to a lower incidence of peripheral neuropathy compared to weekly paclitaxel.
The study enrolled 249 Black patients with stage I to III breast cancer. Patients received either weekly paclitaxel (80 mg/m²) for 12 weeks or docetaxel (75 mg/m²) every 3 weeks for 4 to 6 cycles. The primary endpoint was to prospectively validate germline predictors of taxane-induced peripheral neuropathy (TIPN). Although this endpoint was not met, significant differences were observed in TIPN rates between the treatment arms.
Reduced Neuropathy with Docetaxel
The results showed that 25% of patients treated with docetaxel experienced grade 2 or higher TIPN, compared to 44% of patients in the paclitaxel arm (P = .004). Furthermore, severe (grade 3 or higher) TIPN was less frequent in the docetaxel arm (1.7%) than in the paclitaxel arm (9.4%; P = .011). Dose reductions due to TIPN were also significantly lower in the docetaxel arm (8.5%) compared to the paclitaxel arm (28.1%; P < .001).
"Importantly, the trial did demonstrate significantly less neuropathy and less dose reductions with every-3-week docetaxel compared [with] weekly paclitaxel, suggesting this may be the preferred taxane specifically for Black women with early-stage breast cancer," said lead study author Tarah J. Ballinger, MD, of the Indiana University Melvin and Bren Simon Comprehensive Cancer Center.
Addressing Disparities in Breast Cancer Treatment
Black patients often face disparities in breast cancer treatment, including higher rates of toxicities and worse survival outcomes. Taxane-based therapies, a cornerstone of curative treatment for early-stage breast cancer, can be limited by TIPN. Prior research has indicated that women of African ancestry experience significantly higher rates of TIPN.
"One theme that we have in breast cancer is trying to minimize the toxic effects of some of the treatments. We know that in Black women especially, the risk of developing peripheral neuropathy is increased with taxane[-based therapy]," explained Sunil Adige, MD, assistant professor at the George Washington (GW) Cancer Center.
The EAZ171 study highlights the potential for tailoring chemotherapy regimens to mitigate these disparities. The finding that docetaxel is associated with less neuropathy in Black women compared to weekly paclitaxel could lead to more personalized treatment approaches.
Study Details and Patient Characteristics
The median age of patients was 53 years in the paclitaxel arm and 56 years in the docetaxel arm. The majority of patients had an ECOG performance status of 0 and stage II disease. A significant portion of patients had estrogen receptor–positive/HER2-negative disease (40.8% in the paclitaxel group and 56.9% in the docetaxel group), while triple-negative breast cancer represented 44.8% and 29.3% of the respective groups.
Investigators also examined socioeconomic factors, finding that the majority of patients had completed high school or higher education, and a substantial proportion reported earnings less than $90,000 per year. Most patients had health insurance.
Implications for Clinical Practice
While the study did not validate germline predictors of TIPN, the findings have immediate implications for clinical practice. The data suggest that docetaxel may be the preferred taxane option for Black patients with early-stage breast cancer, potentially reducing the incidence of neuropathy and improving treatment tolerability.
"The biology of the cancer, the genetics of the individual, and the particular characteristics of different racial subgroups is very important [in breast cancer]. We're beginning to understand that [more]," said Sheldon M. Feldman, MD, chief of the Division of Breast Surgery and Breast Surgical Oncology at Montefiore Einstein.
