Under the radar-frequency, timing, duration, and trajectory of lower-grade adverse events in clinical trials of anti-cancer therapies.

importanceThe current methods to capture and report adverse events (AEs) in clinical trials were developed in the era of cytotoxic chemotherapy and typically focused on higher grade AEs which may lead to severe harms. However, current cancer therapies including targeted agents, checkpoint inhibitors, and antibody drug conjugates are commonly administered for a prolonged duration and result in a cumulative symptom burden which may be inadequately reflected by the conventional approach to capture and reporting of AEs. OBSERVATIONS: Existing approaches underestimate the chronic AE burden associated with extended exposure, particularly for low to moderate grade symptomatic AEs, and employ reporting methods that make comparison of similar treatments challenging. Furthermore, the specific AEs that may impact on treatment adherence and lead to dose modifications with oral self‑administered therapy are not typically reported. CONCLUSIONS AND RELEVANCE: To address these limitations, we recommend: (1) a standardized approach to collection and reporting of patient reported AE data for symptomatic AEs, and reporting methods that incorporate information on the longitudinal characteristics of AEs including duration and trajectory; (2) accurately capturing adherence to oral agents; (3) transparent reporting of the AEs that result in dose reduction and treatment discontinuation in trials; (4) adoption of universal structured AE capture and reporting to allow meaningful comparison of the tolerability profile of therapies. As treatment options increase, optimizing capture and reporting of AEs to include lower grade yet troublesome AEs is essential to provide meaningful information on treatment tolerability to inform both clinicians and patients.