Methods: We generated items assessing symptomatic irAEs through a multi-step process of 1) literature review and iterative expert input and 2) qualitative interviews of patients, caregivers, and clinicians regarding ICM-related irAEs and quality of life (QOL) impacts. We administered an initial item set across five longitudinal or cross-sectional studies. We selected a final item set using a Delphi method and evaluated its validity, reliability, minimally important differences (MIDs), and sensitivity to change.
Findings: Findings from qualitative interviews with 14 patients, 7 caregivers, and 6 clinicians informed an initial set of 46 symptomatic irAEs, which was administered to patients (N=503, 52% female, mean age = 64) treated with ICMs for non-small cell lung cancer (n=342), head and neck cancer (n=72), renal cell carcinoma (n=43), or melanoma (n=46) and recruited from an international registry or a comprehensive cancer center. A final irAE item set was selected and mapped to FACIT items, producing the 17-item FACT-ICM Symptom Index (FACT-ICM-17). We examined reliability (α=0.86), construct validity (CFI=0.93), convergent validity with validated measures of physical QOL (r=0.69–0.73), discriminant validity with emotional and social QOL (r=0.03–0.65), and criterion validity (i.e., better performance status was associated with fewer concerns). Response option anchors adequately captured MIDs and were sensitive to change.
Interpretation: This brief FACT-ICM-17 demonstrates construct, convergent, and divergent validity, reliability, MID, and sensitivity to change and is ready for use in research and clinical care.
Funding: Addario/GO2 Lung Cancer Foundation, Florida Biomedical Research Grant (21B12), Prostate Cancer Foundation, P30CA076292, and P30CA008748.
Declaration of Interest: Dr. Kirtane: Owns stock in Veru. Received consulting fees from A2Bio. Scientific advisory board for MyCareGorithm. Dr. Gonzalez: Former consultant for SureMed Compliance. Advisory board member for Elly Health, Inc. Dr. Chung: Received consulting fees from Fulgent, AVEO, Seagen, Exelixis, Genmab, and Regeneron and served in a scientific advisory board for Bicara. Dr. Shafique: Consulting and advisory fees from Jazz Pharmaceuticals and AstraZeneca. Dr. Gray: Consultant/advisor for AbbVie, AstraZeneca, Blueprint Medicines, Coherus, Daiichi Sankyo, Inc (DSI), EMD Serono – Merck KGaA, Gilead Sciences, Inc, IDEOlogy Health, Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Loxo Oncology Inc, Merck & Co., Inc, Novartis, OncoCyte Biotechnology Company, Regeneron, Spectrum ODAC, Takeda Pharmaceuticals, Triptych Health Partners, and Zai Lab (US) LLC. Research support from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, EMD, Serono – Merck KGaA, Genentech, Gilead Sciences, Inc, G1 Therapeutics, Ludwig Institute of Cancer Research, Merck & Co., Inc, Novartis, Panbela Therapeutics, Inc, Pfizer, Regeneron. Dr. Khushalani: Reports consulting/advisory board fees from Regeneron, Merck, Replimune, Immunocore, Iovance Biotherapeutics, Novartis, IO Biotech; Study Steering Committee fees from BMS, Regeneron, Replimune, Nektar; Travel support from Regeneron, Castle Biosciences; Data Safety Monitoring Board for Incyte, AstraZeneca; Scientific Advisory Board for T-Kinfe Therapeutics; Common Stock with Asesnsus Surgical, Bellicum Pharmaceutics, Amarin; Institutional Research Support from BMS, Merck, Novartis, GSK, HUYA Bioscience, Regeneron, Replimune, Celgene, IDEAYA Biosciences, Modulation Therapeutics. Dr. Postow: Reports consulting fees from: BMS, Merck, Novartis, Eisai, Pfizer, Chugai, Erasca, Nektar and Institutional Support from: RGenix, Infinity, BMS, Merck, Novartis, BioAtla, Genentech. Dr. Cella: President of FACIT.org. Ms. Webster: FACIT.org shareholder. Dr. Dicker: Stock and other ownership interests from OncoHost; consulting or advisory role from Janssen, OncoHost, Orano Med, CVS, Aptar Pharma; Travel, accommodations and expenses from OncoHost. Funding from the National Cancer Institute, Prostate Cancer Foundation and the Department of Defense. Dr. Jim: Consultant for SBR Biosciences, grant funding from Kite Pharma. The other authors have no conflicts of interest to disclose.
Ethical Approval: Patient-reported outcomes data were pooled across one qualitative study and four observational studies at Moffitt Cancer Center and combined with clinical and outcomes data collected through retrospective electronic medical record review. Each study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Advarra Institutional Review Board (Pro00019501 on 11/10/2016, Pro00020639 on 2/9/2017, Pro00031908 on 10/9/2017) of Moffitt Cancer Center or deemed exempt from IRB oversight, with ethical review and approval waived due to minimal risk (Pro00048221 on 12/10/2020, Pro00049107 on 1/19/2021). In addition, the GO2 Foundation’s Lung Cancer Registry study was approved by the Center for Disease Control and Prevention (CDC)’s National Health Statistics Reports (NHSR) (PSO-NHSR on 10/13/2017). Informed consent was obtained from all subjects involved in the study.