Effect of cyclooxygenase inhibitor use on immunotherapy efficacy in non-small cell lung cancer

Abstract

Background: A synergistic effect of cyclooxygenase inhibitors (COX-I) and immune checkpoint inhibitors (ICIs) has been suggested. However, the impact of COX-I on the efficacy of ICIs is unclear. Here, we aimed to evaluate the relationship between COX-I use and the efficacy of ICI in patients with non-small cell lung cancer (NSCLC).

Methods: We retrospectively reviewed NSCLC patients who received ICI monotherapy. We defined COX-I use as regular use of COX-I other than low-dose aspirin during the initiation of ICIs to the first evaluation of efficacy. The efficacy of ICIs was evaluated with response rate (RR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Differences in baseline characteristics by COX-I use were controlled by using an inverse probability of treatment weighting (IPW) adjusted analysis.

Results: A total of 198 patients with NSCLC received ICIs; 128, 50, and 20 patients received nivolumab, pembrolizumab, and atezolizumab, respectively; there were 65 (32.8%) COX-I users. While there was no significant difference in RR (15.4% vs. 13.5%; p = 0.828), DCR (41.5% vs. 49.6%; p = 0.294), PFS (median, 2.69 vs. 3.68 months; 95% confidence intervals [CI], 1.77-5.19 vs. 2.20-4.60 months; p = 0.630), COX-I users had significantly shorter OS than non-COX-I users (median, 6.08 vs. 16.10 months; 95% CI: 3.78-11.66 vs. 9.49-19.68 months; p = 0.003). On IPW adjusted analysis, there was no significant difference in OS (median, 7.85 vs. 15.11 months; 95% CI: 5.03-14.92 vs. 9.49-19.32 months; p = 0.081).

Conclusions: There was no additional or negative impact of COX-I use on the efficacy of ICIs in NSCLC.

Keywords: cyclooxygenase inhibitor; immune checkpoint inhibitor; immunotherapy; lung cancer; oncology.