Use of PRO-CTCAE May Help Identify Underreported Adverse Effects in Phase 1 Clinical Trials

Adopting patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) may help better identify adverse events (AEs) that otherwise go underreported, study findings presented at the ESMO Congress 2019 in Barcelona, Spain, have shown. The use of PRO-CTCAE by patients in phase 1 trials revealed that clinician reports of AEs had poor to fair agreement with PRO-CTCAE results.

Although analyses are ongoing, the investigators report that AEs in phase I trial participants may be underreported and suggest an improved tool is needed. A single-center, prospective study was conducted to investigate how well PRO-CTCAE holds up against AEs captured by clinicians compared with patient reported outcome tools among phase I clinical trial participants.

For this investigation, patients eligible for phase I trials were evaluated using tablet-based PRO-CTCAE with an 80-item library. The patients were also evaluated via clinician-reported CTCAE grading of adverse effects at baseline, mid cycle 1, and mid cycle 2.

A total of 292 patients were approached between May 2017 and January 2019.  From that group, 265 patients (91%) consented and 243 (92%) were evaluable. The group was 51% female, the median age was 61 (range, 18 to 82), and 79% were ECOG 1. The most frequent tumor types were gastrointestinal (31.7%), head and neck (13.2%), and breast (10.7%); 66% were treated with immune therapy, 21% with immune and/or targeted therapy, 35% with monotherapy, and 61% with combination therapy.

PRO-CTCAE completion rate was 98.7%. Fatigue (75%), pain (68%), and anxiety (54%) were the most common patient-reported AEs. Those findings were significantly different from the physician reported AEs (fatigue [41%], pain [39%], and insomnia [18%]).

The study showed the overall patient-clinician agreement was poor for fatigue. Similar findings were observed for anxiety and pain. Clinician-reported insomnia was found to be fair. The highest patient-clinician agreement was observed for dyspnea at baseline, and edema and rash at mid cycle 2. Clinician reporting failed to pick up palpitations, hiccups, and vaginal dryness. The clinicians also had poor overall agreement when it came to cognitive symptoms, urinary issues, and mood symptoms.

Reference

Veitch ZW, Shepshelovich D, Gallagher C, et al. Implementation of PRO-CTCAE in phase I clinical trials identifies under reporting of adverse events. Presented at: ESMO Congress 2019; September 27-October 1, 2019; Barcelona, Spain.  Abstract 1755PD.