Article Synopsis

  • Black women have higher rates of taxane-induced peripheral neuropathy (TIPN) when undergoing treatment with paclitaxel, leading to more dose reductions and higher recurrence rates in breast cancer cases compared to White women.
  • The EAZ171 study aimed to validate genetic predictors of TIPN and compare the incidence of TIPN along with dose adjustments between Black women receiving paclitaxel (once weekly) and docetaxel (every three weeks).
  • Results showed that high-risk genotypes did not significantly differ in TIPN occurrences, but those receiving the weekly paclitaxel experienced a higher rate of TIPN and required more dose reductions compared to those on docetaxel.

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Article Abstract

Purpose: Black women experience higher rates of taxane-induced peripheral neuropathy (TIPN) compared with White women when receiving adjuvant once weekly paclitaxel for early-stage breast cancer, leading to more dose reductions and higher recurrence rates. EAZ171 aimed to prospectively validate germline predictors of TIPN and compare rates of TIPN and dose reductions in Black women receiving (neo)adjuvant once weekly paclitaxel and once every 3 weeks docetaxel for early-stage breast cancer.

Methods: Women with early-stage breast cancer who self-identified as Black and had intended to receive (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel were eligible, with planned accrual to 120 patients in each arm. Genotyping was performed to determine germline neuropathy risk. Grade 2-4 TIPN by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was compared between high- versus low-risk genotypes and between once weekly paclitaxel versus once every 3 weeks docetaxel within 1 year. Patient-rated TIPN and patient-reported outcomes were compared using patient-reported outcome (PRO)-CTCAE and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity.

Results: Two hundred and forty of 249 enrolled patients had genotype data, and 91 of 117 (77.8%) receiving once weekly paclitaxel and 87 of 118 (73.7%) receiving once every 3 weeks docetaxel were classified as high-risk. Physician-reported grade 2-4 TIPN was not significantly different in high- versus low-risk genotype groups with once weekly paclitaxel (47% 35%; = .27) or with once every 3 weeks docetaxel (28% 19%; = .47). Grade 2-4 TIPN was significantly higher in the once weekly paclitaxel versus once every 3 weeks docetaxel arm by both physician-rated CTCAE (45% 29%; = .02) and PRO-CTCAE (40% 24%; = .03). Patients receiving once weekly paclitaxel required more dose reductions because of TIPN (28% 9%; < .001) or any cause (39% 25%; = .02).

Conclusion: Germline variation did not predict risk of TIPN in Black women receiving (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel. Once weekly paclitaxel was associated with significantly more grade 2-4 TIPN and required more dose reductions than once every 3 weeks docetaxel.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670807PMC
http://dx.doi.org/10.1200/JCO.24.00526DOI Listing

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