Grant Number:	1R37CA288566-01A1 Interpret this number
Primary Investigator:	Moreno, Patricia
Organization:	University Of Miami School Of Medicine
Project Title:	Symptomatic Toxicities & Quality of Life Among Diverse Individuals Receiving Immune Checkpoint Inhibitors for Metastatic Cancer.
Fiscal Year:	2025

PROJECT SUMMARY Immunotherapy has revolutionized cancer treatment and has become the fourth pillar of cancer care alongside surgery, radiation, and chemotherapy. Immune checkpoint inhibitors work by binding to proteins in order to enable the immune system to recognize and attack cancer cells. Although checkpoint inhibitors offer patients with metastatic solid tumors new options for effective, life-prolonging care, treatment can be accompanied by a host of mild to moderate toxicities and, in some cases, severe or life- threatening immunotherapy-related adverse events (irAES) that cause significant decrements to health-related quality of life (HRQoL). Toxicities vary by ICI class, up to 95% of patients experience at least one toxicity of any grade and between 10% to 47% experience at least one severe (grade 3 or 4) toxicity. Serious irAES like hepatitis, pneumonitis, colitis, and other autoimmune reactions may require immediate management or hospitalization. Toxicities may occur shortly after treatment or emerge as late effects months after treatment. Despite the serious and debilitating consequences of clinician- reported toxicities, limited work has captured patients’ experience on checkpoint inhibitors using patient-reported outcomes (PROs) or identified multilevel predictors and clinical endpoints of symptomatic toxicities and HRQoL in a well-characterized sample of racially, ethnically, and socioeconomically diverse patients. Therefore, the aims of this study are to: Aim 1a) characterize toxicities and HRQoL over time among diverse individuals receiving checkpoint inhibitors for metastatic cancer (N=416) and Aim1b) examine associations with sociodemographic and medical characteristics to identify patient profiles who are at elevated risk for toxicities and decrements in HRQoL; Aim 2) examine potentially modifiable behavioral, psychosocial, and care delivery factors that account for associations between sociodemographic/medical characteristics and toxicities and HRQoL to inform targets of future intervention; Aim 3) examine whether toxicities and HRQoL predict clinical endpoints, including ICI modification, discontinuation, or reinitiation, clinician-reported irAES, cancer progression, death, and healthcare utilization (hospitalization, ED visits, use of oncology nurse triage line). Furthermore, we will use cutting-edge machine learning methods as the basis to create a nomogram prediction tool– the first of its kind that (with future validation) will allow clinicians and patients to estimate a patient’s risk of toxicities and related endpoints using PROs. With our history of successful collaboration, robust immunotherapy programs, and notably diverse catchment areas, the University of Miami Sylvester Comprehensive Cancer Center and UT Health San Antonio Mays Cancer Center are uniquely positioned to conduct this research. In alignment with NCI Moonshot Initiative priorities, this research will generate crucial knowledge to inform intervention efforts to equitably improve the safety and tolerability of checkpoint inhibitors and prevent and mitigate toxicities among diverse patients.





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