Quality of Life Endpoints in Advanced Gastrointestinal Cancer Trials: Systematic Review of Inclusion, Challenges, and...

Advanced gastrointestinal (GI) cancers negatively impact patients' quality of life (QoL). Incorporating QoL endpoints is essential for holistic therapeutic assessment. This systematic review investigated QoL inclusion in advanced GI cancer phase III clinical trials and its associated factors.

A PubMed search identified 3795 articles published between January 2020 and December 2024. After applying inclusion and exclusion criteria, 80 trials evaluating novel agents or dosing regimens were analyzed. Multivariable logistic regression was performed.

Of the 80 trials, 60% included QoL as an endpoint, predominantly as secondary (68.7%) or exploratory (31.3%) endpoints; none incorporated QoL as a primary endpoint. Single-country trials had lower QoL inclusion than multi-country trials (41.9% vs 81.1%; aOR, 0.15, 95% CI, 0.04-0.53; P = 0.003). Studies in journals with impact factors >10 showed greater QoL inclusion (65.4%) compared to those with impact factors <10 (48.0%). Superiority trials had a 61.4% QoL inclusion rate compared to 50.0% in-inferiority trials. QoL inclusion by anatomic location varied, with biliary tract cancers having the highest rates (100%), followed by gastric and GE junction (78.6%), liver (58.8%), colorectal (53.6%), gastric (50.0%), esophageal (40.0%), and pancreatic (25.0%) cancers. Profit-funded trials incorporated QoL assessment more than those non-profit-funded (65.5% vs 45.5%). The EORTC QLQ-C30 was the most frequently used QoL tool, with 75% QoL assessment.

Our systematic review highlights a critical gap in QoL integration. Multi-country trials, those in higher-impact journals, and studies involving biliary tract and gastric cancers demonstrated higher QoL inclusion, emphasizing opportunities to standardize QoL assessments.