Published February 15, 2023
Impact of NSAIDs on Immunotherapy Efficacy in NSCLC
In a recent publication in the journal Clinical Lung Cancer, researchers conducted a retrospective study to examine the correlation between concomitant NSAID use with overall survival (OS) in a real-world cohort of Veterans receiving immune checkpoint inhibitor (ICI) therapy for advanced NSCLC.
Concomitant NSAID usage was defined as the patient picking up a prescription for an NSAID within 90 days before or after ICI administration. Additionally, patients who began an NSAID more than 60 days after the initiation of ICI treatment were eventually excluded. The primary outcome was OS, measured from the start of ICI treatment.
The researchers utilized records from the U.S. Veterans Health Administration Corporate Data Warehouse from 2010 to 2018. They gathered and reviewed data from individuals diagnosed with NSCLC and treated with ICIs.
The researchers concentrated on the four agents FDA-approved for the treatment of NSCLC through 2018, which included nivolumab, pembrolizumab, durvalumab, and atezolizumab.
The study included 3,634 patients with NSCLC who were receiving ICIs, 2,336 (64.3%) of whom were exposed to concomitant NSAIDs. The patients receiving concomitant NSAIDs were most frequently treated with two or more NSAIDs (40.2%), aspirin (32.0%), ketorolac (10.3%), ibuprofen (6.3%), or diclofenac (4.3%).
The authors wrote, “To our knowledge, this is the first study of a real-world cohort that provides clinical evidence of an association between NSAIDs and concomitant immunotherapy with improved overall survival in NSCLC patients.”
The results revealed that in a univariate analysis, concomitant use of NSAIDs with ICIs was correlated with enhanced OS when compared with the use of ICIs alone, and the reported median OS was 10 months and 8 months, respectively (hazard ratio [HR], 0.87; 95% CI, 0.81-0.94; P <.01).
The authors noted that other factors linked with enhanced OS included chemotherapy during or after ICI, older age, African American race, lower comorbidity burden, adenocarcinoma histology, earlier disease stage, earlier year of diagnosis, and longer time from diagnosis to ICI.
In a multivariate analysis (HR, 0.83; 95% CI, 0.76-0.89; P <.01), concomitant use of NSAIDs was also associated with enhanced OS. The same factors mentioned above were also correlated with enhanced OS.
The researchers reported that when patients were stratified by the type or number of NSAIDs received, only diclofenac (HR, 0.60; 95% CI, 0.47-0.77; P <.01) and two or more NSAIDs (HR, 0.75; 95% CI, 0.68-0.83; P <.01) had a statistically significant correlation with overall OS.
The authors noted that due to the correlation of diclofenac, particularly with OS, researchers also performed a subset analysis to compare patients who received diclofenac with those who did not receive NSAIDs. Patients who received diclofenac had significantly enhanced OS in a univariate analysis (HR, 0.65; 95% CI, 0.51-0.83; P <.01) and a multivariate analysis (HR, 0.62; 95% CI, 0.48-0.79; P <.01).
Propensity score matching of the original cohort generated 1,251 patients per cohort balanced in characteristics, and NSAIDs continued to be linked with enhanced OS (HR, 0.85; 95% CI, 0.78-0.92; P <.001).
The authors concluded, “In summary, we identified an association of improved overall survival with ICI and NSAID use. This may indicate that NSAIDs can enhance ICI-induced antitumor immunity, potentially through COX [cyclooxygenase] inhibition or distinct antitumor pathways. These findings merit prospective study.”
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