Factors affecting symptom presentation in an early-phase clinical trials clinic patient population
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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.
KeywordsPatient reported outcome Clinical trial Symptom ECOG performance status Adolescent and young adult (AYA)
We acknowledge Laura L. Russell from The University of Texas MD Anderson Cancer Center’s Scientific Publications team for her editorial assistance.
Preparation of this report was funded in part by the Hawn Foundation and RO1CA242565.
Compliance with ethical standards
Conflict of interest
GCG declares that she has no conflict of interest. TRM declares that he has no conflict of interest. ECI declares that she has no conflict of interest. MM declares that she has no conflict of interest. SFA declares that she has no conflict of interest. CSC declares that he has no conflict of interest. SAP reports grants from NIH/NCI during the conduct of the study; other from AbbVie, Inc., Aminex Therapeutics, BioMarin Pharmaceutical, Inc., Boehringer Ingelheim, BristolMyers Squib, Cerulean Pharma Inc., Chugai Pharmaceutical Co., Ltd., Curis, Inc., Five Prime Therapeutics, Genmab A/S, GlaxoSmithKline, Helix BioPharma Corp., Incyte Corp., Jacobio Pharmaceuticals Co., Ltd., Medimmune, LLC., Medivation, Inc., Merck Sharp and Dohme Corp., NewLink Genetics Corporation/Blue Link Pharmaceuticals, Novartis Pharmaceuticals, Pieris Pharmaceuticals, Inc., Pfizer, Principia Biopharma, Inc., Puma Biotechnology, Inc., Rapt Therapeutics, Inc., Seattle Genetics, Taiho Oncology, Tesaro, Inc., TransThera Bio, XuanZhu Biopharma, Amphivena Therapeutics, Inc., outside the submitted work. AT reports research funding: IMMATICS, Parker Institute for Cancer Immunotherapy, Tempus, EMD Serono; Baxalta; Foundation Medicine; ONYX; Bayer; Boston Biomedical; Placon Therapeutics; Karus Therapeutics; Tvardi; OBI Pharma. Consulting or Advisory Role: Tempus, Roche, Covance, Genentech. Dr. Naing reports grants from NCI; EMD Serono; MedImmune; Healios Onc. Nutrition; Atterocor; Amplimmune; ARMO BioSciences; Eli Lilly; Karyopharm Therapeutics; Incyte; Novartis; Regeneron; Merck; BMS; Pfizer, CytomX Therapeutics; Neon Therapeutics; Calithera Biosciences; TopAlliance Biosciences; Kymab; PsiOxus; Immune Deficiency Foundation (Spouse), other from CytomX Therapeutics; Novartis, other from ARMO BioSciences, outside the submitted work. DSH reports grants from Bayer, Lilly, Genentech, LOXO, Pfizer, Amgen, Mirati, Ignyta, Merck, Daichii-Sanko, Eisai, Adaptimmune, Abbvie, Astra-Zeneca, BMS, Genmab, Infinity, Kite, Kyowa, Medimmune, Molecular Template, Novartis, Takeda; personal fees from Mirna, LOXO, Bayer, Baxter, Guidepoint global, Oncoresponse, Janssen, Molecular Match, outside the submitted work.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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