Factors affecting symptom presentation in an early-phase clinical trials clinic patient population

• Authors: Goldy C George, University of Texas MD Anderson Cancer Center; Tito R Mendoza, University of Texas MD Anderson Cancer Center; Eucharia C Iwuanyanwu, University of Texas MD Anderson Cancer Center; Meryna Manandhar, Rollins School of Public Health; SolmazF Afshar, University of Texas MD Anderson Cancer Center; Sarina A Piha-Paul, University of Texas MD Anderson Cancer Center; Apostolia Tsimberidou, University of Texas MD Anderson Cancer Center; Aung Naing, University of Texas MD Anderson Cancer Center; Charles S Cleeland, University of Texas MD Anderson Cancer Center; David S Hong, University of Texas MD Anderson Cancer Center
• Journal Title: Investigational New Drugs
• Volume: Volume 38, Number 4
• Publisher: Springer Nature | 2020-08-01, Pages 1166-1174
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1007/s10637-019-00879-0
• Subjects: Health Sciences, Oncology; Health Sciences, Public Health
• Keywords: Adolescent and young adult (AYA); Clinical trial; ECOG performance status; Patient reported outcome; Symptom; Adolescent; Adult; Aged; Antineoplastic Agents; Clinical Trials, Phase I as Topic; Female; Humans; Male; Middle Aged; Neoplasms; Patient Reported Outcome Measures; Severity of Illness Index; Symptom Assessment; Young Adult

Abstract

Increasing numbers of oncology therapies are being approved based on early-phase single-arm studies. Yet, little is known regarding the use of patient-reported outcomes in single-arm oncology trials testing novel therapies. We examined patient-reported symptom severity and symptom interference with activity- (WAW: work, general activity, walking) and mood-(REM: relations with others, enjoyment of life, mood) related functioning, and their association with factors known to influence symptom severity reporting, in early-phase clinical trials clinic patients. Patients completed the validated MD Anderson Symptom Inventory, containing 13 severity items and six interference items, each rated on a 0–10 scale (higher scores = worse symptom severity/interference). Performance status (ECOG-PS) and age were ascertained. Multiple linear regression was performed. In 248 phase I patients (51% female, 90% ECOG 0–1, and 74% ≤65 years), 67% of patients had ≥seven concurrent symptoms of any severity level, and 51% of patients described ≥three concurrent symptoms as moderate-to-severe (severity rating ≥ 5). Composite symptom severity, WAW and REM were worse in patients with ECOG-PS ≥ 2 vs. 0–1, and worse in patients with ECOG-PS = 1 than in patients with ECOG-PS = 0. Compared with patients over 65y, adolescent and young adult (AYA) patients (18y-39y) and patients aged 40y to 65y had worse composite symptom severity. As expected, being employed full-time/retired was associated with better symptom profiles in phaseI patients. The variation of symptom burden by performance status and age suggest that these factors need to be considered in the design of early-phase trials, particularly if patient-reported symptoms are used as primary/secondary/exploratory endpoints.