Association of HBsAg Positivity and HBV Reactivation in EGFR-Mutant Lung Adenocarcinoma Treated with EGFR-TKIs: A Retrospective Cohort Study

Background: EGFR-TKIs serve as standard first-line targeted therapy for EGFR-mutant lung adenocarcinoma (LUAD). Real-world data on the prognostic role of baseline HBsAg positivity and the risk of HBV reactivation during EGFR-TKI treatment remain limited, particularly in HBV-endemic Chinese populations. Methods: This retrospective single-center cohort study enrolled 580 consecutive patients with stage III–IV EGFR-mutant LUAD who received EGFR-TKIs between 2013 and 2026. Patients were grouped by baseline HBsAg status; Kaplan–Meier curves and multivariable Cox models adjusted for key clinical covariates were used to evaluate progression-free survival (PFS) and overall survival (OS). HBV reactivation was defined by EASL criteria, with virological evaluation available for 51 of 82 HBsAg-positive patients. Results: Among all enrolled patients, 14.1% were HBsAg-positive. The HBV reactivation rate was 9.8% among evaluable HBsAg-positive patients, and reactivation was not independently linked to survival. After adjustment, baseline HBsAg positivity showed a borderline trend toward poorer OS (HR = 1.42, 95% CI, 0.99–2.04, p = 0.054) without significant PFS association (HR = 1.14, 95% CI, 0.80–1.62, p = 0.481). Liver metastasis independently predicted worse OS in HBsAg-positive patients (HR = 3.84, 95% CI, 1.65–8.94, p = 0.002). Conclusions: HBV reactivation was uncommon but warrants close monitoring during EGFR-TKI therapy. Baseline HBsAg positivity demonstrated only a non-significant trend toward inferior OS without affecting PFS. Routine HBsAg screening at diagnosis may facilitate risk stratification, and HBsAg-positive patients with liver metastasis require intensified surveillance.