Opioid use and overdose in patients with solid tumor cancers

Importance — Opioids are essential for symptom control, but few studies have evaluated the association between prescription opioids and opioid overdose in oncology.

Objective — To describe opioid overdose in adults with solid tumor cancers and examine how opioid overdose rates vary by patient factors, cancer characteristics, and opioid prescribing.

Design, setting, and participants — This population-based, retrospective cohort study of adults in Ontario, Canada, used linked ICES data from January 1, 2013, to December 31, 2020. Participants entered the cohort at the time of newly diagnosed solid tumor cancers and were followed up from diagnosis to the first opioid overdose event, death, or December 31, 2024. Data analysis was performed from August to December 2025.

Exposure — Exposure was outpatient opioid prescription dose and duration reassessed every 30 days.

Main outcomes and measures — The primary outcome was a fatal or the first nonfatal opioid overdose event.

Results — Among 554 316 adults with cancer (mean [SD] age, 63.8 [16.2], 57.1 [17.2], and 45.8 [13.7] years for the no, nonfatal, and fatal opioid overdose groups, respectively; 308 903 [55.9%], 921 [59.5%], and 116 [60.7%] female for the no, nonfatal, and fatal opioid overdose groups, respectively), 1591 (0.3%) had 1 or more nonfatal opioid overdoses, and 191 (0.03%) had a fatal opioid overdose. In the first year after diagnosis, patients with stage III and IV cancers had substantially higher rates of any opioid overdose than those with stage I (stage III vs I: hazard ratio [HR], 2.55; 95% CI, 1.96-3.31; stage IV vs I: HR, 6.24; 95% CI, 4.68-8.31). After adjustment, any opioid prescription in the prior 30 days was associated with 71% higher combined nonfatal and fatal opioid overdose rate (HR, 1.71; 95% CI, 1.47-2.00), and approximately 3.5 times higher if prescribed high-dose opioids (≥50-mg morphine-equivalent daily dose; HR, 3.47; 95% CI, 2.97-4.05). Recently prescribed opioids were associated with increased opioid overdose risk in patients with cancer without opioid use disorder (any dose: HR, 1.80; 95% CI, 1.54-2.11; high dose: HR, 3.76; 95% CI, 3.21-4.41).

Conclusions and relevance — In this cohort study of adults with solid tumor cancers, opioid overdose was rare and highest in the first year after diagnosis and in patients with advanced cancer; opioid overdose risk increased with every month high-dose opioids were prescribed. The findings suggest that opioids should be prescribed at the lowest effective dose for symptom management, with close monitoring and routine assessment for opioid overdose risk.