Differential survival impact of acetaminophen and non-steroidal anti-inflammatory drugs on NSCLC patients undergoing immune checkpoint inhibitor therapy: a region-wide cohort study in Hong Kong, China

Lung cancer remains the leading cause of cancer-related mortality worldwide.1 Immune checkpoint inhibitors (ICIs) have substantially improved survival outcomes in non-small cell lung cancer (NSCLC).However, treatment benefit remains heterogeneous, and durable responses are limited to a subset of patients.2 In routine clinical practice, ICIs are frequently administered together with supportive medications, and the potential impact of commonly used non-opioid analgesics on immunotherapy outcomes remains incompletely characterized.Acetaminophen (APAP) and non-steroidal anti-inflammatory drugs (NSAIDs) are both recommended as first-line non-opioid analgesics for cancer-related pain and fever and are commonly regarded as clinically interchangeable in supportive care guidelines.3 Consequently, these agents are often prescribed interchangeably during ICI treatment based primarily on symptom control.However, because the efficacy of ICIs depends on effective antitumor immune activation, the long-standing assumption that APAP and NSAIDs are clinically equivalent in the immunotherapy setting has rarely been explicitly examined and therefore warrants closer scrutiny.Existing clinical and translational evidence suggests that APAP and NSAIDs may differentially interact with antitumor immunity.Clinical cohort evidence indicates that detectable plasma APAP levels are associated with poorer outcomes in patients treated with ICIs. 4 In contrast, NSAIDs have been proposed to modulate antitumor immunity through