Landscape review of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in oncology: Adoption and recent learnings.
Authors: Regnault Antoine , Quéré Stephane , Gorsh Boris , Sapra Sandhya , Loubert Angély , Davis Randy , Nelsen Linda , Cardellino Anna , Eliason Laurie 
Published: June 2021

e18587 Background: The PRO-CTCAE is a patient-reported outcome measure of symptomatic toxicity in oncology trials designed to complement CTCAE criteria (clinician’s measure of adverse events [AEs]). Items for evaluation are selected from 78 symptomatic toxicities in the CTCAE. PRO-CTCAE uptake and use has not been uniformly assessed; understanding how to best analyze and present PRO-CTCAE data is important. We reviewed literature on clinical trials reporting the PRO-CTCAE to ascertain its use and current analytical methods to inform future analyses. Methods: A review of the literature and ongoing oncology trials using PubMed, oncology and outcomes research conferences (ASCO, ASH, ISOQOL, ISPOR), and ClinicalTrials.gov was completed August 2019; updated November 2020. Selected literature included guidance on: item selection; analytical methods; PRO-CTCAE data/endpoint use in clinical trials. Analytical and visualization methods from the literature were used to inform the specification of PRO-CTCAE analyses conducted on data from the DREAMM-2 (NCT03525678) trial of single-agent belantamab mafodotin (belamaf; BLENREP), a B-cell maturation antigen–binding antibody–drug conjugate, in relapsed/refractory multiple myeloma. Results: After screening (n = 197), 45 articles were reviewed: 13 related to recommendations for use/analysis, 7 to item selection, and 25 to examples of PRO-CTCAE use. 118 completed/ongoing trials reported PRO-CTCAE use (17 [14%] Phase I or I/II; 73 [62%] Phase II, II/III, or III; 3 [3%] Phase IV; 25 had no phase reported). Most (92/118, 78%) trials included the PRO-CTCAE as a secondary endpoint. The number of trials using the PRO-CTCAE increased from 3 in 2015 to 30 in 2020. PRO-CTCAE data in the literature were reported descriptively using tables (maximum post-baseline ratings; mean change over time; ratings higher than a predefined cutoff) and graphs (line graphs; stacked bar charts; heatmaps). These and more sophisticated analyses were applied to DREAMM-2 data to best capture the dynamics of patient-reported AEs over time, or control for baseline PRO-CTCAE ratings (eg, Toxicity over Time approach; ordinal log-linear models). Conclusions: The importance of tolerability and symptomatic AEs for patients is increasingly recognized, particularly for new therapies. This landscape review demonstrates recent growth in interest and adoption of PRO-CTCAE. There are few existing standards for analysis; this research increases understanding of existing methods and further evaluates ways of analyzing and presenting PRO-CTCAE data over time. Additional research exploring innovative methods to analyze PRO-CTCAE data and address its challenges is needed. Funding Source: GlaxoSmithKline (212225). Drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa.