Prognostic Impact of Concomitant Beta-Blocker Use on Survival in EGFR-Mutant Metastatic Non-Small Cell Lung Cancer Patients Treated with Erlotinib

<i>Background and Objectives</i>: Erlotinib, a tyrosine kinase inhibitor (TKI), is an established therapy for patients with metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Preclinical and clinical evidence suggests that chronic stress, mediated through β-adrenergic signaling, promotes tumor progression, angiogenesis, and therapy resistance. Furthermore, interactions between β-adrenergic signaling and EGFR pathways have been hypothesized to negatively influence treatment responses. Based on this rationale, we investigated whether concomitant beta-blocker use may improve survival outcomes in EGFR-mutant NSCLC patients treated with erlotinib. <i>Materials and Methods</i>: This retrospective analysis included 103 patients with metastatic EGFR-mutant NSCLC who received erlotinib. Patients were classified according to concurrent beta-blocker use, defined as continuous therapy for at least six months prior to erlotinib initiation, prescribed for cardiovascular indications. Progression-free survival (PFS) and overall survival (OS) were compared between beta-blocker users and non-users. <i>Results</i>: Patients receiving erlotinib with concomitant beta-blocker therapy achieved a median PFS (mPFS) of 21.4 months (95% CI, 13.1-29.7), compared with 9.7 months (95% CI, 6.7-12.7) in non-users (<i>p</i> = 0.003). Median OS (mOS) was 32.4 months (95% CI, 14.8-50.0) in the beta-blocker group versus 19.9 months (95% CI, 14.8-25.0) in the non-beta-blocker group (<i>p</i> = 0.010). Multivariate Cox regression confirmed beta-blocker use as an independent prognostic factor for both PFS (<i>p</i> = 0.004) and OS (<i>p</i> = 0.014). <i>Conclusions</i>: Concomitant beta-blocker use was associated with significantly prolonged survival in patients with EGFR-mutant metastatic NSCLC receiving erlotinib. These findings support the hypothesis that β-adrenergic inhibition enhances the efficacy of EGFR-targeted therapy. Prospective studies are warranted to validate these results and to further elucidate the underlying biological mechanisms.