The potential impact of H1 antihistamines on clinical outcomes in NSCLC patients undergoing EGFR‐TKIs treatment

Abstract

Background Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR‐TKIs) have substantially improved outcomes in non‐small cell lung cancer (NSCLC); however, the development of treatment resistance remains a major clinical challenge. This study examines the association between concomitant prescriptions of H1‐antihistamines (H1AHs) and clinical outcomes in NSCLC patients undergoing EGFR‐TKIs therapy. Methods We conducted a retrospective cohort study using the Taipei Medical University Clinical Research Database (TMUCRD) linked to the Taiwan Cancer Registry. Patients with advanced NSCLC receiving EGFR‐TKI therapy between 1 January 2008 and 31 December 2022 were classified according to concomitant prescription of H1AHs. The primary and secondary endpoints were time to treatment failure (TTF) and all‐cause mortality, respectively. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Sensitivity analyses and landmark analyses were performed to evaluate the robustness of the findings. Results Among 828 eligible patients, 475 (57.37%) received concomitant H1AHs during EGFR‐TKIs therapy, whereas 353 (42.63%) did not. Concomitant prescriptions of H1AHs exhibited a significantly reduced risk of treatment failure (aHR; 0.61, 95% CI; 0.53–0.71, p < .001), corresponding to longer mean TTF (2.09 vs . 1.25 years), as well as a lower risk of all‐cause mortality (aHR; 0.36, 95% CI; 0.30–0.44, p < .001). A stronger association was observed in patients with extended durations of H1AHs exposure (≥60 or ≥90 days). Conclusions Concomitant prescriptions of H1AHs with EGFR‐TKIs therapy were associated with a significantly reduced risk of treatment failure and mortality in patients with advanced NSCLC.