Longitudinal patient-reported outcomes on genotype-guided irinotecan dosing: feasibility and clinical relevance

• Published in: The oncologist (Dayton, Ohio) Ohio), 2024-09, Vol.29 (9), p.780-785
• Main Authors: Sorah, Jonathan D, Deal, Allison M, Stein, Sophia I, Jonsson, Mattias, Innocenti, Federico, Turk, Anita, Boles, Jeremiah C, Irvin, William, Basch, Ethan M, Sanoff, Hanna K, Wood, William A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer patients; Clinical Relevance; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Feasibility Studies; Female; Gastrointestinal Cancer; Genetic aspects; Genotype; Humans; Irinotecan - administration & dosage; Irinotecan - therapeutic use; Longitudinal Studies; Male; Medical research; Medicine, Experimental; Metastasis; Middle Aged; Patient outcomes; Patient Reported Outcome Measures
• ISSN: 1083-7159; 1549-490X; 1549-490X
• DOI: 10.1093/oncolo/oyae121

Abstract Introduction Standard investigator-based adverse events (AE) assessment is via CTCAE for clinical trials. However, including the patient perspective through PRO (patient-reported outcomes) enhances clinicians’ understanding of patient toxicity and fosters early detection of AEs. We assessed longitudinal integration of PRO-CTCAE within clinical workflow in a phase II trial. Materials and methods As a sub-study in a phase II trial of genotype-directed irinotecan dosing evaluating efficacy in patients with metastatic colorectal cancer receiving FOLFIRI and bevacizumab, patients reported on 13 AEs generating a PRO-CTCAE form. The primary objective was to estimate forms completed by patients and clinicians at least 80% of time. Secondary objectives were estimating concordance and time to first score of specific symptoms between patient and clinician pairs. Results Feasibility of longitudinal PRO-CTCAE integration was met as 96% of patients and clinician-patient pairs completed at least 80% of PRO-CTCAE forms available to them with 79% achieving 100% completion. Concordance between patient and clinician reporting a severe symptom was 73% with 24 disconcordant pairs, 21 involved patients who reported a severe symptom that the clinician did not. Although protocol-mandated dose reductions were guided by CTCAE not PRO-CTCAE responses, the median time to dose reduction of 2.53 months, and the time-to-event curve closely approximated time to patient-reported toxicity. Conclusion Longitudinal integration of PRO-CTCAE paired CTCAE proved feasible. Compared to clinicians, patients reported severe symptoms more frequently and earlier. Patient-reported toxicity more closely aligned with dose decreases indicating incorporation into routine clinical practice may enhance early detection of toxicity improving patient safety and quality of life. This study showed that patient-reported outcomes are feasible, implementable in the context of a clinical trial, and allow patients the opportunity to report toxicity earlier which likely leads to earlier detection of effects on quality of life and improved patient safety.