<scp>Coronavirus disease 2019</scp> infection reduces <scp>EGFR</scp> ‐ <scp>TKI</scp> efficacy in non‐small cell lung carcinoma: Real‐world evidence from a multicenter propensity‐matched cohort

Coronavirus disease 2019 (COVID-19) remains a global health threat, particularly for patients with cancer, who experience greater susceptibility and worse outcomes. Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is standard first-line therapy for advanced EGFR-mutated non-small cell lung carcinoma (NSCLC). However, the impact of COVID-19 on TKI efficacy remains unclear. This multicenter retrospective study included patients with stage IV EGFR-mutated NSCLC who received first-line EGFR-TKI treatment at four Chinese hospitals. Leveraging China's policy change (December 2022), we compared a pre-pandemic COVID-19-negative cohort (January 2019-November 2022) with a COVID-19-positive cohort (January-June 2023). After 1:1 propensity score matching (PSM), Kaplan-Meier and Cox regression analyses evaluated progression-free survival (PFS) and prognostic factors. Among 711 patients (median follow-up, 37.90 months), the COVID-19-negative group had significantly longer median PFS (18.17 vs. 12.89 months; p = .001). After PSM, we analyzed 426 well-matched patients (213/cohort). Before and after matching, COVID-19-negative patients exhibited better PFS with all EGFR-TKI generations (unmatched: p_1st <.001, p_2nd = .030, and p_3rd = .001; matched: p_1st <.001, p_2nd = .049, and p_3rd = .015). COVID-19 infection worsened outcomes in both monotherapy and combination therapy. Multivariable analysis identified COVID-19 infection as an independent predictor of worse PFS (hazard ratio 1.650, 95% confidence interval: 1.286-2.116; p < .001). Adenocarcinoma, ≤3 metastatic organs, smoking index >570, concurrent systemic therapy, and third-generation TKI were also prognostic. COVID-19 infection markedly reduces EGFR-TKI efficacy in patients with advanced NSCLC, warranting closer monitoring during and after infection and supporting adaptive management strategies.