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Life sciences · Journal article
BMC Medicine · October 21, 2026
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The clinical benefit of adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with completely resected non-small cell lung cancer (NSCLC) harboring major uncommon EGFR mutations remains uncertain. We evaluated the efficacy of adjuvant EGFR-TKIs and explored outcomes according to TKI generation and mutation subtype. Patients with completely resected NSCLC harboring major uncommon EGFR mutations, including G719X, S768I, L861Q, or compound major uncommon mutations, treated between 2020 and 2023 were retrospectively reviewed. Patients receiving adjuvant EGFR-TKIs were compared with those managed without TKIs. Baseline imbalances were adjusted using inverse probability of treatment weighting (IPTW). Disease-free survival (DFS) was the primary endpoint. Among 154 eligible patients, 46 (29.9%) received adjuvant EGFR-TKIs and 108 (70.1%) did not. Median follow-up was 45.1 months (interquartile range 33.5–58.3). After IPTW adjustment, adjuvant EGFR-TKI therapy was associated with improved 3-year DFS compared with no TKI therapy (73.6% vs. 53.0%; p = 0.018). Multivariable Cox analysis identified adjuvant TKI therapy as an independent protective factor for DFS (adjusted hazard ratio: 0.42; p = 0.006). The association appeared more evident in patients with stage III disease (hazard ratio: 0.26; p = 0.006). Third-generation TKIs were associated with longer DFS than earlier-generation agents (3-year DFS 83.7% vs. 52.7%; p = 0.010). Adjuvant EGFR-TKIs were associated with prolonged DFS in completely resected NSCLC with major uncommon EGFR mutations. The observed benefit appeared more pronounced in stage III disease and among patients receiving third-generation TKIs. These findings are exploratory and support prospective evaluation of adjuvant EGFR-TKI therapy in this rare molecular subgroup.