BackgroundChemotherapy-induced peripheral neuropathy (CIPN) compromises function and quality of life (QoL) and may precipitate chemotherapy modification. We evaluated longitudinal Patient-reported outcome measures (PROMs) during duloxetine-based CIPN management and explored clinical predictors of response.MethodsThis secondary longitudinal analysis was conducted within a randomized clinical cohort receiving duloxetine-based therapy for chemotherapy-induced peripheral neuropathy (CIPN). Of the patients included in the parent trial, 72 with analyzable patient-reported outcome data were included in the present analysis. PROMs were collected at baseline, week 4, and week 8 using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Chemotherapy-Induced Peripheral Neuropathy 20-item module (EORTC QLQ- CIPN20), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx), Brief Pain Inventory (BPI), and Hamilton Anxiety Rating Scale HAM-A, and were analyzed using generalized estimating equations with multivariable adjustment. Instruments included EORTC QLQ-CIPN20 (0–100; higher = worse), FACT/GOG-Ntx (higher = better), Brief Pain Inventory (BPI) severity and interference (0–10; higher = worse), and. Hamilton Anxiety Rating Scale (HAM-A; higher = worse).ResultsIn this PROM analysis, significant improvement was observed across CIPN symptoms, pain, anxiety, and QoL outcomes over 8 weeks. QLQ-CIPN20 total decreased at week 4 (MD −12.64) and week 8 (MD −23.81) versus baseline (both p < 0.001), with sensory (−13.71; −26.45), motor (−10.97; −22.06), and autonomic (−9.00; −18.44) domain reductions (all p < 0.001). FACT/GOG-Ntx increased in week 4 (MD +6.42) and week 8 (MD +7.46) (p < 0.001), with no significant week 4-to-week eight increment. HAM-A decreased (−3.42; −6.77), while BPI severity (−1.55; −2.78) and interference (−1.26; −2.60) improved (all p < 0.001). Higher baseline pain predicted worse CIPN, lower QoL, and higher anxiety; metastatic disease and chemotherapy dose reduction were associated with poorer outcomes; missingness showed no strong baseline predictors.ConclusionDuloxetine-based management was associated with rapid, sustained improvement in CIPN symptoms, pain, anxiety, and QoL over 8 weeks, supporting risk-stratified supportive care pathways.