Participation of older patients with advanced gastroesophageal cancer in clinical trials: A systematic review of age-restrictive inclusion criteria over the last 25 years.

Abstract

e24017 Background: Cancer is a disease of aging, however older patients are underrepresented in the clinical trials that determine the standards of care for oncological treatment. We conducted a review to identify whether there have been age-restrictive inclusion criteria in clinical trials over the last twenty five years. We focused on patients with metastatic gastroesophageal cancer. Methods: A search strategy was developed encompassing Embase, Pubmed and The Cochrane Library databases. All completed Phase III randomised controlled trials evaluating systemic anti-cancer therapies in metastatic gastroesophageal malignancies for the period 01.01.95 to 18.11.20 were identified. Reference management software (Covidence; Veritas Health Innovation Ltd) was used to screen for inclusion/exclusion. The following details were extracted from trial protocols: country of study, date of publication, patient number, age inclusion and exclusion criteria. The median age of participants and the percentage of older patients enrolled in each study was collected. A linear probability model was used to estimate the change over time in the proportion of studies using an upper age exclusion. Results: 363 phase III studies were identified. 152 studies were eligible for full text review, 86 were excluded, leaving 66 trials for final analysis. 86% (n = 56) included Gastric, 9% (n = 6) Oesophageal and 5% (n = 3) Oesophagogastric malignancies. Asian studies represented 48% (n = 32) of trials, 29% (n = 19) were worldwide and 23% (n = 15) were European. The median age of trial participants was 62, (range 18-94). No clear trend in the ages of study participants over the time period was identified. 32% (n = 21) of studies specified an upper age limit for inclusion and 57% of these were Asian studies. The median age of exclusion was 75 years (range 65-80). All studies starting before 2003 used an upper age exclusion (n = 12); whereas only 9 of the 52 that started in 2003 or later did (17%). Among these later studies, there was a very modest downward yearly-trend in the proportion of studies using an upper age exclusion (-0.02 per year; 95%CI -0.05 to 0.01; p = 0.31). 52% (n = 34) of studies specified the proportion of their study population who were over 65 years. Older patients represented only 36% of the trial populations in these studies (range 7-60%). Our search of currently enrolling trials on clinicaltrials.gov yielded 11 active studies, none of which specified an upper age limit. Conclusions: Recent years have seen improvements in clinical trial protocols, with many no longer specifying restrictive age criteria. Reasons for poor representation of older patients are complex and ongoing efforts are needed to broaden eligibility criteria and prioritise the inclusion of older adults in clinical trials.