BACKGROUND: Older adults with advanced cancer are at higher risk of treatment-related toxicities, which can impair function. Relationships between clinician-rated and patient-reported toxicities with functional decline remain unclear. METHODS: This secondary analysis of the GAP70+ trial aimed to evaluate the associations between clinician-rated (Clinician-rated common Terminology Criteria for Adverse Events [CTCAE]) and patient-reported toxicities (PRO-CTCAE) with changes in physical performance and functional outcomes in older adults receiving systemic therapy. Physical performance was measured using the Short Physical Performance Battery (SPPB
impairment: score ≤9). Functional capacity was assessed using activities of daily living (ADL) and instrumental ADL (IADL)
impairment: any task difficulty. Toxicities were captured by CTCAE and PRO-CTCAE, which assess symptom severity and activity interferences. Generalized estimating equations evaluated the association of toxicity grades (0-1, 2, ≥3) within 3 months of treatment initiation with new functional impairments within 6 months. RESULTS: Patients were age 70 to 96 years. At baseline, 82.9% had impaired SPPB, 51.5% had impaired IADL, and 27.4% had impaired ADL. Among patients without baseline impairments, 57.7%, 47.4%, and 31.0% developed new SPPB, IADL, and ADL impairments, respectively. No association was found between CTCAE toxicity and new SPPB impairment (p = .70), but higher PRO-CTCAE toxicity severity (p = .02) and interference (p = .02) were associated with new SPPB impairments. New IADL impairments were more common with higher grades of CTCAE (p = .02) severe PRO-CTCAE toxicities (p = .02). CONCLUSION: These findings emphasize the need to assess both clinician-rated and patient-reported toxicities to understand and mitigate functional decline in older adults with advanced cancer.