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

Abstract

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 [OR], 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 multivariable Cox regression analysis, opioid use was associated with worse OS among patients with pancreatic cancer (hazard ratio [HR], 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.

Opioid Prescriptions and Survival in Pancreatic Cancer

“…Notably, as the authors discuss, their findings contradict previous data from other retrospective analyses, which found opioid use correlated with worse survival in patients with advanced gastrointestinal cancer and specifically PDAC. 14,15 Thus, future work will need to confirm the findings from the current study with prospective designs, potentially including randomized trials of earlier symptom management for patients with PDAC. Additionally, interpreting retrospective cohort studies requires particular care to avoid several biases, including selection bias.…”

Opioid Prescription Is Associated With Increased Survival in Older Adult Patients With Pancreatic Cancer in the United States: A Propensity Score Analysis

“…5 However, the inclusion of clinical trial participants may have led to inadvertent confounding by their use of novel therapies. 5 Another study found worse survival in 90 male patients with pancreatic cancer who received opioids, although this analysis focused on gonadal status, which may affect survival. 13 Studies by Steele et al and Oh et al assessing survival among patients who received opioids found that patients who required higher opioid doses had shorter survival.…”

“…Future studies should continue to investigate the role of opioids and the effect of measures to mitigate pain and symptom management on pancreatic cancer survival. Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY3 Geriatric Research, Education and Clinical Center, James J. Peters VA Medical Center, Bronx, NY4 Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, NY5 Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY6 Division of Gastroenterology, University of Miami Leonard Miller School of Medicine, Miami, FL CORRESPONDING AUTHOR Aimee L. Lucas, MD, MS, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1069, New York, NY 10029; e-mail: aimee.lucas@mssm.edu.DISCLAIMERThe views expressed in this article are those of the authors and do not necessarily reflect the positions or policies of the Department of Veterans Affairs or the United States Government.…”

Pancreatic Cancer and Microenvironments: Implications of Anesthesia

“…Steele et al reported that high opioid use was associated with decreased survival (adjusted HR = 2.76; 95% CI: 1.39–5.48) in newly diagnosed stage IV PC [ 66 ]. Abdel-Rahman et al also reported that opioid use was associated with worse overall survival (HR, 1.245; 95% CI, 1.063–1.459; P = 0.007) in patients with PC [ 67 ]. Call et al showed that intraoperative opioid use was not associated with decreased survival in PC surgery [ 68 ].…”