Feasibility of frequent monitoring of symptoms using the PRO-CTCAE in the NRG-BR004 clinical trial.

Background: The PRO-CTCAE Measurement System was designed to enhance the quality of the standard toxicity evaluation in clinical trials. We developed a substudy within NRG-BR004, a phase III clinical trial in patients with newly documented HER2-positive metastatic breast cancer (MBC), to examine the added value and feasibility of frequent PRO-CTCAE data collection.

Methods: Patients were asked to complete 23 PRO-CTCAE items assessing 12 symptoms. Electronic PRO (ePRO) reporting was preferred; however, paper administration was allowed. The data on items assessed before treatment initiation, then weekly during Cycles 1-2 (12 weeks), are presented herein. Feasibility of frequent assessment with ePRO reporting was assessed using these data and was predefined as ≥25% of patients being compliant (submitted ≥75% of scheduled assessments). We also examined PRO-CTCAE and clinician-reported CTCAE data for key symptoms using maximum toxicity grade and the toxicity index (TI).

Results: Overall, 80% of patients (82 of 103) were compliant with expected weekly assessments (90% CI = 0.72 to 0.86). For all symptoms, the median maximum grade (TI value) of clinician-reported CTCAE was lower than the median maximum score (TI value) of patient-reported PRO-CTCAE. The differences in the data trend for weekly vs less frequent assessment were more apparent when data were evaluated using the TI vs the maximum score.

Conclusions: Weekly assessments within the first two chemotherapy cycles were feasible in this trial of MBC patients. As expected, patients reported greater severity of symptoms than clinicians. Demonstrating the feasibility of frequent assessment could have implications for future research and clinical practice.

Clinicaltrials.gov: NCT03199885 (https://clinicaltrials.gov/study/NCT03199885).