Nodal Status And Patient-Reported Health Status Are Key Determinants Of Palbociclib Treatment Discontinuation In Early Breast Cancer: An Analysis From The PALLAS (AFT-05; ABCSG-42) Trial.Registrations: Clinicaltrials.Gov: NCT02513394, Eudract: 2014-005181-30

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Abstract
Background: In adjuvant HR+/HER2− breast cancer, tolerability and persistence with long-term therapy are critical. In PALLAS, adding palbociclib to endocrine therapy (ET) did not improve invasive disease-free or overall survival. We investigated factors associated with treatment intolerance and early discontinuation.Patients and methods: This exploratory analysis evaluated early palbociclib discontinuation among patients initiating planned two-year palbociclib plus ET in PALLAS. Competing-risks methods and cause-specific hazard models assessed associations between baseline demographic, clinical, and patient-reported outcome (PRO) measures and discontinuation for reasons other than recurrence or death. Dose reductions, treatment-emergent toxicities, and longitudinal PRO trajectories were also evaluated.Results: Among 2,840 patients initiating palbociclib plus ET, 1,171 (41.3%) discontinued palbociclib early. Dose reductions to 100 mg and 75 mg occurred in 55.2% and 33.6%, respectively. In multivariable analysis, higher nodal stage was associated with lower discontinuation risk (N3 versus N0: HR 0.59, 95% CI 0.45–0.79), whereas poor baseline overall quality of life (HR 1.87, 95% CI 1.10–3.19) and financial difficulties (HR 1.27, 95% CI 1.05–1.54) were independently associated with increased risk. Similar patterns were observed for dose reductions. Patients discontinuing within three months were older, less likely to have received chemotherapy, and had more baseline PRO impairments, particularly anxiety. Baseline PRO impairment was also associated with treatment-emergent toxicities, particularly non-haematological events. Longitudinally, fatigue and nausea were more prominent with palbociclib.Conclusions: Baseline patient-reported health status, nodal stage, and socioeconomic factors are important determinants of adjuvant palbociclib discontinuation. Integrating PROs into treatment decision-making and monitoring may help identify patients at increased risk of treatment intolerance and support more individualised management of prolonged adjuvant therapy.