(A-131) Medications with anti-inflammatory mechanisms and risk of non-small cell lung cancer (NSCLC): A population-based case-control study in the US using SEER-Medicare data

Background: Lung cancer is the leading cause of cancer death globally. Effective prevention strategies may significantly reduce incidence and mortality. Emerging evidence suggests anti-inflammatory medications may offer preventive benefits by modulating pathways involved in lung carcinogenesis.

Objectives: To evaluate whether commonly prescribed anti-inflammatory medications are associated with NSCLC risk.

Methods: We conducted a population-based, case-control study using the SEER-Medicare database. Cases were Medicare beneficiaries diagnosed with NSCLC as their first primary cancer (index date) between 2012 and 2019, aged ≥70 years at diagnosis. For each case, up to 4 controls were selected from beneficiaries without NSCLC on July 1st of the diagnosis year matched on age, sex, ethnicity, race, and state of residence, with ≥5 years of continuous enrollment of Medicare Part A, B and D without enrollment of an HMO. Prescription anti-inflammatory medication exposure was assessed over 5 years prior to and excluding 60 days before the index date by claims. Exposure was categorized as binary and also by duration of use. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for smoking history and comorbidities. Associations were further stratified by COPD status.

Results: Pooling 42,289 NSCLC cases and 162,490 controls, the median age date was 77 years, ~56% were female, 82% were non-Hispanic white with African Americans (6.3%), Hispanics (5.8%), and Asian/Pacific Islanders (5.3%). Cases were more likely to have peripheral vascular disease (39% vs. 31%), COPD (53% vs. 34%), and smoking history (63% vs. 43%) compared to controls but were similar in other comorbidities. Use of corticosteroids (adjusted OR: 0.85, 95% CI: 0.82-0.87) and immune cell targeting medications (adjusted OR: 0.86, 95% CI: 0.81-0.91) were associated with a statistically significant reduced risk of NSCLC, while disease-modifying anti-rheumatic medications were associated with an increased risk (adjusted OR: 1.16, 95% CI: 1.10-1.24) compared to no use. Longer duration of use was associated with a larger reduction in risk for both corticosteroids and immune cell targeting medications (p < 0.001). COX-1/2 inhibitors were marginally or not associated with NSCLC risk. Consistent risk reduction was seen in patients with and without COPD for both drug types.

Conclusions: This population-based study suggests that corticosteroids and immune cell targeting medications are associated with lower NSCLC risk in older adults. These findings warrant further studies to confirm these associations in diverse populations and to explore underlying biological mechanisms.