Abstract 585P
Background
Early phase oncology trials establish the safety of novel anti-cancer agents. However, clinician-assessed toxicity gradings may miss up to half of adverse events compared to patient reported events, leading to an incomplete picture of a drug’s tolerability. There is growing interest in PROs to enhance toxicity reporting and improve patient representation in drug development. However, little is known about PRO use in this setting. This study describes trends and characteristics of PRO use in early phase oncology trials.
Methods
Trials with a dose escalation component registered on ClinicalTrials.gov to commence from 01/01/2007- 20/01/2020 with ‘PROs’ or ‘health-related quality of life’ as an outcome were extracted. Search results were screened to confirm inclusion criteria were met. Study and PRO characteristics were extracted. Descriptive analysis was used to describe trends in PRO usage.
Results
548 studies were identified. 231 (42.2%) were eligible: adult (224, 97%), paediatric (7, 3%), solid tumour (176, 75.9%), haematology (56, 24.1%), seamless phase I/II (108, 46.8%). Maximum tolerated dose (MTD) (107, 35%) and safety (95, 31%) were the most common primary endpoints. The majority involved drug combinations (119, 51.5%) with targeted therapy (94, 40.7%), immunotherapy (33, 14.3%) and radiotherapy (33, 14.3%) in escalation. PRO use tripled (9 to 29 studies), with an average increase of 2.3/year (95% CI: 1.6-2.9) from 2007- 2019. The number of countries sponsoring PRO studies increased (3 to 11 studies). PROs were typically used in academic-sponsored studies (135, 58.4%) and as a secondary endpoint (209, 89.7%). Most used 1 PRO measure (range 1-7). PROs were collected during dose escalation (114, 49.1%) or phase I/II (54, 23.3%). The most common PRO measures were the EORTC QLQ C30 (81, 21.3%) and EQ-5D-5L (19, 5%).
Conclusions
Although PRO use has increased over time in a wider variety of settings, its use remains limited. This study will inform a survey of trialists from academia and industry to assess attitudes to PROs and their potential to define tolerable doses and regimens. Further work is necessary to determine how to integrate PROs into dose-finding trials and generate guidelines to standardise their use and reporting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Julia Lai-Kwon.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.