Outcomes of Patients With Advanced Gastrointestinal Cancer in Relationship to Opioid Use: Findings From Eight Clinical Trials

Background: This study assessed the patterns of opioid use among patients with advanced gastrointestinal cancers who were included in 8 clinical trials and evaluated the impact of opioid use on survival outcomes of included patients. Methods: Deidentified datasets from 8 clinical trials evaluating first-line systemic treatment of advanced gastrointestinal cancers were accessed from the Project Data Sphere platform (ClinicalTrial.gov identifiers: NCT01124786, NCT00844649, NCT00290966, NCT00678535, NCT00699374, NCT00272051, NCT00305188, and NCT00384176). These trials evaluated patients with pancreatic carcinoma, gastric carcinoma, hepatocellular carcinoma (HCC), and colorectal carcinoma. Multivariable logistic regression analysis was used to evaluate factors predicting the use of opioids. Kaplan-Meier survival estimates were used to compare survival outcomes in each disease entity among patients who did or did not receive opioid treatment. Multivariable Cox regression analysis was then used to further assess the impact of opioid use on survival outcomes in each disease entity. Results: A total of 3,441 participants were included in the current analysis. The following factors predicted a higher probability of opioid use within logistic regression analysis: younger age at diagnosis (odds ratio [On 0.990; 95% CI, 0.984-0.997; P=.004), nonwhite race (OR for white vs nonwhite, 0.749; 95% CI, 0.600-0.933; P=.010), higher ECOG score (OR for 1 vs 0, 1.751; 95% CI, 1.490-2.058; P<.001), and pancreatic primary site (OR for colorectal vs pancreatic, 0.241; 95% CI, 0.198-0.295; P<.001). Use of opioids was consistently associated with worse overall survival (OS) in Kaplan-Meier survival estimates of each disease entity (P=.008 for pancreatic cancer; P<.001 for gastric cancer, HCC, and colorectal cancer). In muftivariable Cox regression analysis, opioid use was associated with worse OS among patients with pancreatic cancer (hazard ratio [HRI, 1.245; 95% CI, 1.063-1.459; P= .007), gastric cancer (HR, 1.725; 95% CI, 1.403-2.122; P<.001), HCC (HR, 1.841; 95% CI, 1.480-2.290; P<.001), and colorectal cancer (HR, 1.651; 95% CI, 1.380-1.975; P<.001). Conclusions: Study findings suggest that opioid use is consistently associated with worse OS among patients with different gastrointestinal cancers. Further studies are needed to understand the underlying mechanisms of this observation and its potential implications.