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

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.