Taxane-Induced Peripheral Neuropathy-Driven Treatment Modification and Pathologic Complete Response After Neoadjuvant TCHP in HER2-Positive Breast Cancer: A Retrospective Cohort Study.

BACKGROUND

Neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) is a widely used regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, achieving high rates of pathologic complete response (pCR). Taxane-induced peripheral neuropathy (CIPN) represents a clinically relevant dose-limiting toxicity that may lead to premature taxane discontinuation. Evidence guiding the optimal neoadjuvant strategy after CIPN onset remains limited in real-world, toxicity-driven treatment modification scenarios.

PATIENTS AND

METHODS

We conducted a retrospective cohort study including patients with HER2-positive breast cancer treated with neoadjuvant TCHP at a single institution. Peripheral neuropathy was assessed during routine clinical care and graded according to Common Terminology Criteria for Adverse Events v6.0. Among patients who developed clinically significant CIPN prompting modification of the planned neoadjuvant regimen, the analysis focused on this subset (nested cohort), in whom postneuropathy management consisted of either taxane discontinuation without anthracycline switch (taxane-discontinuation strategy) or switching to an anthracycline-based regimen (TCHP → AC). The primary endpoint was pCR, defined as absence of invasive disease in breast and axillary lymph nodes (ypT0/is ypN0). Multivariable logistic regression was used to evaluate the association between postneuropathy strategy and pCR, adjusting for prespecified clinicopathologic covariates. Prespecified stratified analyses were performed according to hormone receptor (HR) status, Ki-67 category, and clinical nodal status.

RESULTS

Among 843 patients treated with neoadjuvant TCHP, 180 (21.4%) developed CIPN that prompted treatment modification. Of these, 96 patients were managed with the taxane-discontinuation (nonanthracycline) strategy and 84 with the TCHP → AC strategy. pCR was achieved in 25.0% of patients in the taxane-discontinuation (nonanthracycline) strategy group compared with 64.3% in the TCHP → AC group (P = .001). In multivariable analysis, switching to an anthracycline-based regimen after CIPN was independently associated with a higher likelihood of achieving pCR compared with taxane discontinuation alone (adjusted odds ratio 5.21, 95% confidence interval 2.11-14.82; P = .001). The direction and magnitude of this association were consistent across prespecified subgroups, with no significant interaction observed according to HR status, Ki-67, or clinical nodal status.

CONCLUSION

In this large real-world cohort of HER2-positive breast cancer treated with neoadjuvant TCHP, switching to an anthracycline-based regimen after taxane-induced peripheral neuropathy was associated with a markedly higher probability of achieving pCR compared with taxane discontinuation alone. These findings support a pragmatic, efficacy-preserving strategy for patients unable to complete taxane therapy due to CIPN and address a clinically relevant gap not directly covered by current treatment guidelines.