Patient-Reported Outcomes in Early-Phase Oncology Clinical Trials: A Stepping Stone to a Patient-Centered Drug Development.

Abstract

In phase I clinical trials, the recommended phase II dose (RP2D) is usually set at or near the maximum tolerated dose (MTD), which is determined based on the observation of dose-limiting toxicities (DLTs). Clinicians typically evaluate toxicities using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), with grade three or higher toxicities classified as DLTs. However, it has been repeatedly demonstrated that physicians tend to underestimate patient's symptoms. Therefore, patient-reported outcomes (PROs), especially the NCI PRO-CTCAE questionnaire, can complement clinician assessments by providing direct patient input on adverse events. This integration could lead to a more accurate definition of DLT and better informed RP2D decisions. Moreover, PROs could optimize sample size strategies in later-stage trials and enable comparison of health-related quality of life (HRQoL) data with synthetic control arms to confirm the benefit of a drug, especially in rare oncogene-driven subsets. Whilst stakeholders and regulatory authorities acknowledge the value of integrating PROs early in drug development, they emphasize the lack of methodological guidelines to support broader adoption. The integration of PROs represents an opportunity to improve the patient-centeredness of phase I trials, ultimately strengthening the drug development process.