Nonsteroidal anti-inflammatory drugs (NSAIDs) may improve the efficacy of immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC), according to a retrospective study.
Researchers found that NSCLC patients who received NSAIDs within 90 days of ICI administration had longer overall survival (OS), compared with those who received ICIs alone. The results were published in Clinical Lung Cancer.
Using records from the US Veterans Health Administration Corporate Data Warehouse, researchers examined data from individuals diagnosed with NSCLC and treated with ICIs from 2010 through 2018. The researchers focused on the 4 agents approved for use in NSCLC through 2018 — nivolumab, pembrolizumab, durvalumab, and atezolizumab.
For study purposes, the researchers defined concomitant NSAID use as the patient picking up a prescription for an NSAID within 90 days before or after ICI administration. However, patients who started an NSAID more than 60 days after the start of ICI treatment were ultimately excluded. The primary outcome was OS, measured from the start of ICI treatment.
The study included 3634 patients with NSCLC receiving ICIs, 2336 (64.3%) of whom were exposed to concomitant NSAIDs. Patients receiving concomitant NSAIDs were most commonly treated with 2 or more NSAIDs (40.2%), aspirin (32.0%), ketorolac (10.3%), ibuprofen (6.3%), or diclofenac (4.3%).
In a univariate analysis, concomitant use of NSAIDs with ICIs was associated with improved OS compared with use of ICIs alone. The median OS was 10 months and 8 months, respectively (hazard ratio [HR], 0.87; 95% CI, 0.81-0.94; P <.001).
Concomitant use of NSAIDs was also associated with improved OS in a multivariate analysis (HR, 0.83; 95% CI, 0.76-0.89; P <.001).
When patients were stratified by the type or number of NSAIDs received, only diclofenac (HR, 0.60; 95% CI, 0.47-0.77; P <.001) and 2 or more NSAIDs (HR, 0.75; 95% CI, 0.68-0.83; P <.001) were significantly associated with OS.
Researchers also conducted a subset analysis to compare patients who received diclofenac with those who did not receive NSAIDs. Patients who received diclofenac had significantly improved OS in a univariate analysis (HR, 0.65; 95% CI, 0.51-0.83; P <.001) and a multivariate analysis (HR, 0.62; 95% CI, 0.48-0.79; P <.001).
“In summary, we identified an association of improved overall survival with ICI and NSAID use,” the researchers concluded. “This may indicate that NSAIDs can enhance ICI-induced antitumor immunity, potentially through COX inhibition or distinct antitumor pathways. These findings merit prospective study.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Sebastian NT, Stokes WA, Behera M, et al. The association of improved overall survival with NSAIDs in non-small cell lung cancer patients receiving immune checkpoint inhibitors. Clin Lung Cancer. Published online January 20, 2023. doi:10.1016/j.cllc.2022.12.013