ABSTRACT Introduction Anti‐inflammatory agents including acetaminophen (APAP) and non‐steroidal anti‐inflammatory drugs (NSAIDs) may blunt anti‐tumor immunity. Methods We performed a patient‐level cross‐trial analysis of five randomized controlled studies (IMpower110, IMpower130, IMpower131, IMpower132, and IMpower150) that assessed the efficacy of first‐line atezolizumab therapy in advanced non‐small cell lung cancer (NSCLC). We investigated whether APAP/NSAIDs exposure influenced progression‐free survival (PFS) and overall survival (OS) in both atezolizumab‐treated and non‐atezolizumab‐treated cohorts using forest plot analysis. Results In 3781 patients, APAP exposure was 15.4% (583/3781) and NSAIDs use was 33.9% (1282/3781). APAP use was associated with worse PFS and OS in both the atezolizumab and non‐atezolizumab groups (PFS with atezolizumab: hazard ratio HR = 1.18, 95% confidence interval CI: 0.97–1.43; PFS without atezolizumab: HR = 1.23, 95% CI: 1.05–1.43; OS with atezolizumab: HR = 1.13, 95% CI: 0.98–1.30; OS without atezolizumab: HR = 1.31, 95% CI: 1.04–1.65). NSAIDs use was not associated with differences in PFS or OS in the atezolizumab group but was linked to worse PFS and OS in the non‐atezolizumab group (PFS with atezolizumab: HR = 0.98, 95% CI: 0.89–1.08; PFS without atezolizumab: HR = 1.18, 95% CI: 1.03–1.34; OS with atezolizumab: HR = 1.01, 95% CI: 0.91–1.13; OS without atezolizumab: HR = 1.27, 95% CI: 1.10–1.46). After excluding patients on baseline proton pump inhibitors, a significant interaction between NSAIDs use and treatment modality was observed in the multivariable analysis of OS ( p = 0.0140), with no interaction for APAP use ( p = 0.6707). Conclusion Neither APAP nor NSAIDs exposure influenced atezolizumab efficacy.
Takada et al. (Fri,) studied this question.
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