Effect of polypharmacy and potentially inappropriate medications on physical functional decline among older adults with advanced cancer receiving systemic treatment

Polypharmacy and potentially inappropriate medications (PIM) are common among older adults with advanced cancer, but their association with physical functional outcomes is understudied. This study aimed to estimate the risk of physical functional decline associated with medication measures in older adults with advanced cancer starting a new line of systemic treatment.

This secondary analysis of GAP 70+ Trial (PI: Mohile) enrolled patients aged 70+ with advanced cancer, had ≥ 1 geriatric assessment domain impairment and planned to start a new antineoplastic regimen with a high risk of toxicity. Polypharmacy (concurrent use of ≥ 8 medications (meds)) was assessed before initiation of treatment. PIM were categorized using Screening Tool of Older Person’s Prescriptions (STOPP) criteria and 2019 Beers criteria. Physical functional outcomes were assessed within 3 months of treatment initiation: (1) Activity of Daily Living (ADL) decline: 1-point decrease in ADL score between baseline and 3 months; (2) Instrumental ADL (IADL) decline: 1-point decrease in IADL score between baseline and 3 months; (3) Short physical performance battery (SPPB) decline, defined as 1-point decrease on SPPB; (4) ≥ 1 falls within 3 months of treatment. Separate multivariable, cluster-weighted Generalized Estimating Equations models adjusted for relevant covariates (e.g., age, baseline function/comorbidities).

Among 616 participants, mean number of meds was 6 (range 0–24); 28% received ≥ 8 meds. Polypharmacy was associated with increased risk of ADL decline (adjusted risk ratio [aRR], 1.31; 95% CI, 1.00–1.71). Taking ≥ 1 PIM per STOPP was associated with increased risk of IADL decline (aRR, 1.21; 95% CI, 1.04–1.40) and falls (aRR, 1.93; 95% CI, 1.49–2.51).

In a large cohort of vulnerable older adults with advanced cancer receiving systemic treatment, polypharmacy and PIM were independently associated with an increased risk of physical functional decline. This emphasizes the need to develop interventions to optimize medication use, intending to improve outcomes in these patients.

ClinicalTrials.gov Identifier: NCT02054741. Registered 01–31-2014.