Patient reported outcomes in anti-PD-1/PD-L1 inhibitor immunotherapy registration trials: FDA analysis of data submitted and future directions.

Abstract

Patient-reported outcome measures can be used to capture the patient's experience with disease and treatment. Immunotherapy agents including the anti-programmed death receptor-1/programmed death-ligand-1 inhibitor therapies have unique symptomatic side effects and patient-reported outcome data can help to characterize the benefits and burdens associated with therapy. We reviewed registration trials in the Food and Drug Administration database for five anti-programmed death receptor-1/programmed death-ligand-1 inhibitor therapies to characterize trial design and patient-reported outcome assessment strategy (cutoff 31 December 2017). We evaluated the patient-reported outcome measurement coverage of eight key symptoms related to adverse events reported in immunotherapy agent product labels (fatigue, diarrhea, cough, shortness of breath, musculoskeletal pain, rash, pruritus, and fever). There were a total of 28 trials across seven disease types and one tumor agnostic indication reviewed, of which 17 were randomized and 25 were open label. Of the 28 trials, 21 contained patient-reported outcome measures and all 21 used >1 instrument. The most common instruments were the EuroQol five dimension (N = 19), and the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (N = 17). Disease-specific patient-reported outcome tools were included in nine trials (six lung, one head and neck, one melanoma and one renal cell). No trial used a patient-reported outcome strategy assessing all eight selected adverse events. Collection of patient-reported outcome data in anti-programmed death receptor-1/programmed death-ligand-1 inhibitor trials were variable and did not consistently assess important symptomatic adverse events. Use of a patient-reported outcome instrument with well-defined functional scales supplemented by item libraries to incorporate relevant symptomatic adverse events may allow for improved understanding of the patient experience while receiving therapy. These data, along with other clinical data such as hospitalizations and supportive care medication use can help inform the benefit-risk assessment for regulatory purposes.