Beyond Misuse: AEs and Opioids in Older Cancer Survivors

Harms Are Not All Sensational

Sharon Worcester

September 22, 2020

Ongoing opioid use by older breast cancer patients in the year after cancer treatment was associated with an increased risk for drug-related adverse events (AEs), but events related to opioid misuse were less common than more pedestrian problems such as gastrointestinal and cardiovascular events, infections, and falls/fractures, new research indicates.

Adverse drug events related to substance misuse, such as overdose, occurred at a rate of 0.010 per 1000 person-days in 38,310 women in the Surveillance, Epidemiology and End Results (SEERS)-Medicare database.

However, the rates for other (ie, non-misuse) adverse events associated with opioid use and for all-cause hospitalization were much higher at 0.237 and 0.675 per 1000 person-days, respectively, report Aaron N. Winn, PhD, of the Medical College of Wisconsin in Milwaukee, and colleagues.

In the current study, the less sensational AEs were 20-fold more common that those associated with misuse, note the authors, who also explain that although opioids are still a mainstay of pain management in cancer patients, evidence increasingly suggests their actual use for cancer pain is limited.

The new findings underscore concerns about the use of opioids in this population as they demonstrate a significantly increased risk for "multiple preventable serious adverse drug events," they said, urging clinicians to recognize that "opioid-related risks in this population extend beyond misuse, overdose, and opioid use disorder."

The study was published online September 15 in JAMA Network Open.

The investigators reviewed data from fee-for-service Medicare beneficiaries ages 66 to 90 years who were diagnosed with stage 0 to III breast cancer from January 2008 through December 2015.

Notably, on days in which women had opioid exposure, things got worse.

An adjusted analysis, controlling for patient demographics, clinical factors, and characteristics of cancer diagnosis and treatment, showed a "consistent positive association between current opioid exposure and serious adverse drug events," the authors note.

Current opioid exposure was associated with "significantly higher" adjusted risk for all AEs (compared with risk on days without opioid exposure): 14.62 for adverse drug events related to opioid misuse, 2.50 for all other adverse drug events related to opioid use, and 2.77 for all-cause hospitalization.

"The risks of [gastrointestinal] events, infection, falls and fractures, and cardiovascular events were 2- to 3-fold higher on days with current opioid exposure," the authors commented, adding that a dose-response effect was observed.

High daily opioid doses were consistently associated with higher risk of all study outcomes, compared with low doses; compared with days of no opioid exposure, ≥50 mg and 1-49 mg morphine-equivalent doses per day were associated with more than a 3- and 2-fold higher risk for an AE related to substance misuse (aRRs, 3.40 and 2.29, respectively).

Focus on Prevention

Ongoing national efforts to improve safe opioid prescribing focus on preventing misuse, overdose, and opioid use disorder, but don't directly address opportunities to better prevent other serious opioid-related harms in at-risk populations such as older adults who may have an increased risk for events not related to misuse, assert the authors.

"Clinicians should carefully weigh the benefits and comprehensive risk of opioid therapy in older adult survivors of breast cancer who have completed active breast cancer treatment," the authors conclude.

One potential approach to judicious decision-making regarding opioid prescribing in cancer survivors is in identifying risk factors, as reported by Medscape Medical News.

A 2019 study assessed rates of posttreatment opioid use, rates of opioid abuse or dependence, and admissions for opioid toxicity. Subsequent models using patient demographic, cancer, and treatment factors showed high levels of discrimination in identifying those at risk for opioid-related adverse outcomes such as persistent opioid use (area under the curve = 0.85), an opioid abuse or dependence diagnosis (AUC = 0.87), and admission for opioid abuse or toxicity (AUC = 0.78).

Cancers treated with more intensive, multimodal therapies — including esophageal, pancreatic, liver, head and neck, and lung cancer — had the highest adjusted risk for persistent opioid use, and prior opioid use was highly associated with future chronic use (72.2% vs. 1.5% rates of future chronic use for prior opioid user vs opioid-naive patients who did not receive a prescription during treatment).

Other factors associated with increased risk included younger age, employment status, smoking history, and a prior depression or drug abuse history, reported the authors of that 2019 study, led by Lucas K. Vitzthum, MD, Department of Radiation Medicine and Applied Science at the University of California, San Diego. Factors identified that haven't been previously reported included race, income, alcohol use, comorbidities, body mass index, and cancer type.

"Improved risk stratification will allow for personalized risk assessment and improve the safety of pain management in cancer survivors," concluded Vitzthum and colleagues, adding that future work is needed to externally validate their models, ideally in a prospective setting.

The study was supported by the National Center for Advancing Translational Sciences, the National Institute on Minority Health and Health Disparities, and the American Cancer Society. Winn reported receiving grants from the "Advancing a Healthier Wisconsin Endowment" during the conduct of the study. Coauthor Joan Neuner reported receiving grants from the National Institutes of Health during the conduct of the study.  

JAMA Netw Open. Published online September 15, 2020. Full text

Sharon Worcester is a reporter for MDedge News, part of the Medscape Professional Network.

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