Treatment-Limiting Taxane-Induced Peripheral Neuropathy: Timing, Severity and Clinical Predictors in Patients...

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and clinically significant neurotoxicity associated with taxane-based chemotherapy, which is frequently leading to treatment modification or discontinuation. In the neoadjuvant setting, treatment-limiting CIPN may compromise the delivery of planned therapy. However, detailed data on the timing, severity and clinical predictors of severe CIPN remain limited, particularly in real-world populations.

We conducted a retrospective single-institution cohort study including consecutive patients with HER2-positive breast cancer treated with neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP). The analysis was restricted to patients who developed CIPN requiring discontinuation of docetaxel. Neuropathy severity was graded according to CTCAE v6.0 and categorized as grade 2 or grade 3. Clinical variables associated with severe neuropathy were evaluated using Firth penalized logistic regression.

Among 843 patients treated with neoadjuvant TCHP, 180 (21.4%) developed treatment-limiting CIPN and were included in the analysis. Grade 3 neuropathy occurred in 32 patients (17.8%). Severe CIPN was associated with higher body mass index, diabetes mellitus, pre-existing peripheral neuropathy and cardiovascular comorbidities. Neuropathy frequently developed early during treatment, with a substantial proportion of severe cases occurring within the first two cycles or present at baseline. Patients with grade 3 CIPN received fewer cycles of chemotherapy, reflecting early treatment discontinuation.

Treatment-limiting CIPN during neoadjuvant taxane-based therapy is often an early event and is strongly associated with patient-related vulnerability factors, particularly metabolic and neurologic comorbidities. These findings support the need for early risk stratification and closer neurologic monitoring in patients at increased risk for severe neurotoxicity.