Assessment of quality-of-life inclusion in phase III clinical trials for advanced gastrointestinal cancers: A 2020–2024 systematic review.

e23185 Background: Metastatic and advanced gastrointestinal (GI) cancers negatively impact patients' lifespans and quality of life (QoL). As clinical trials explore novel treatment strategies, including patient-reported QoL as an endpoint is essential for holistic therapeutic assessment. This study investigated the extent of QoL inclusion in Phase III clinical trials involving metastatic and advanced GI malignancies and analyzed factors associated with QoL inclusion. Methods: We conducted a systematic review. A PubMed search identified 3,795 articles published between January 2020 and December 2024. After applying inclusion and exclusion criteria, 80 Phase III clinical trials evaluating novel agents or dosing regimens were analyzed and cross referenced with clinicaltrials.gov. Extracted data included QoL endpoints (primary, secondary, exploratory, or not analyzed), the use of EORTC QLQ-C30, study design, masking, funding source, multi-country involvement, study result, anatomical location, histological subtype, publication year, journal impact factor, and class of therapy. We performed chi-squared tests, followed by multivariable logistic regression to examine factors associated with QoL inclusion. Results: Of the 80 trials, 60% (n = 48) included QoL as an endpoint, predominantly as secondary (68.7%) or exploratory (31.3%) endpoints, whereas none included QoL as a primary endpoint. Trials conducted in a single country had lower QoL inclusion rates than those in multiple countries (41.9% vs 81.1%, AOR: 0.15, 95% CI: 0.04–0.53, P = .003). Studies in journals with impact factors > 10 showed greater QoL inclusion (65.4%) compared to journals with impact factors < 10 (48.0%). Superiority designs dominated (87.5%), with 61.4% incorporating QoL, whereas non-inferiority trials had 50% incorporation. Blinded trials assessed QoL more frequently (69.2%) compared to open-label studies (55.6%). 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 frequently (65.5%) than non-profit-funded studies (45.5%). Study results did not significantly impact QoL assessment (positive: 61.5% vs. negative: 57.1%, P = .702). The EORTC QLQ-C30 was the most frequently used QoL tool, applied in 75% of trials assessing QoL. Conclusions: Our systematic review found that 40% of Phase III GI cancer trials excluded QoL, highlighting a critical gap in the integration of patient-reported outcomes. 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 across all trials.