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

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02054741. Registered 01-31-2014.

Development and Evaluation of a Multisource Approach to Extend Mortality Follow-Up for Older Adults With Advanced Cancer Enrolled in Randomized Trials.

PURPOSE: Mortality data can complement primary end points from cancer clinical trials. Yet, identifying deaths after trial completion is challenging, as timely and comprehensive vital status data are unavailable in the United States. We developed and evaluated a multisource approach to capture death data after clinical trial completion. METHODS: Individuals age 70 years and older with incurable solid tumors or lymphoma and ≥1 aging-related condition were enrolled from October 2014 to March 2019 (ClinicalTrials.gov identifier: NCT02107443 and NCT02054741). Participants provided consent to link trial information to external sources. We developed a stepped approach for extended death capture using (1) active trial follow-up up to 1 year, (2) linkage to the National Death Index (NDI), and (3) obituary searches, thus generating a 5-year survival curve. In a random sample of 50 participants who died during trial follow-up, we estimated sensitivity of death data using NDI and obituary sources and computed survival times by data source. RESULTS: The two trials enrolled 1,169 participants; mean age was 76 years; 46% were female; and gastrointestinal cancer (30%) and lung cancer (26%) were the most common cancer types. Across data sources, maximum follow-up was >7 years; 5-year survival was 18%. In total, there were 841 deaths: 603 identified during trial follow-up; 199 from the NDI; and 39 from obituary searches. The sensitivity for death capture was 92% for the NDI and 94% for the obituary searches compared with the trial data, and computed survival times were similar across data sources. CONCLUSION: Extending clinical trial mortality follow-up through linkage with external data sources was feasible and accurate. Future cancer clinical trials should collect necessary consent and patient identifiers for vital status linkages that can enhance understanding of longer-term outcomes.