Research report: Adjuvant EGFR-TKI therapy in completely resected non–small cell lung cancer with major uncommon EGFR mutations: a real-world study

Patients with completely resected non-small cell lung cancer harboring major uncommon epidermal growth factor receptor mutations had longer disease-free survival when they received adjuvant EGFR tyrosine kinase inhibitor therapy, according to a retrospective real-world study. The analysis included 154 eligible patients treated between 2020 and 2023: 46 received an EGFR tyrosine kinase inhibitor after surgery and 108 did not. After inverse probability of treatment weighting to address baseline imbalances, estimated three-year disease-free survival was 73.6% in the treated group and 53.0% in the untreated group, with a p-value of 0.018.

The study focused on an evidence gap in which the clinical benefit of adjuvant EGFR tyrosine kinase inhibitors for these molecularly defined tumors remained uncertain. Eligible cancers carried G719X, S768I, L861Q, or compound major uncommon EGFR mutations. Disease-free survival was the primary endpoint, and median follow-up was 45.1 months, with an interquartile range of 33.5 to 58.3 months.

Multivariable Cox proportional-hazards analysis identified adjuvant EGFR tyrosine kinase inhibitor therapy as an independent protective factor for disease-free survival. Because this was an observational analysis, the result does not establish that the medication caused the improved outcome. The association appeared stronger among patients with stage III disease.

In that subgroup, the reported hazard ratio was 0.26, with a p-value of 0.006. The stage-specific estimate should therefore be treated as exploratory rather than as evidence of a proven subgroup effect. Outcomes also differed according to inhibitor generation.

Patients receiving a third-generation EGFR tyrosine kinase inhibitor had an estimated three-year disease-free survival rate of 83.7%, compared with 52.7% among those receiving an earlier-generation agent; the difference had a p-value of 0.010. This comparison represents an observed association and does not show that third-generation therapy directly produced the longer survival. Several features of the study limit the strength and generalizability of its conclusions.

It was a retrospective cohort study rather than a randomized trial, and treatment was not assigned at random. The comparison groups had baseline imbalances, which the investigators addressed through inverse probability of treatment weighting. The results support further prospective evaluation of adjuvant EGFR tyrosine kinase inhibitors after complete resection of non-small cell lung cancer with major uncommon EGFR mutations.

The improved disease-free survival estimates, together with the stage III and third-generation subgroup associations, identify promising patterns for investigation. They do not yet establish the superiority of a particular inhibitor generation, confirm a stage-specific treatment effect, or determine whether the observed associations will persist under controlled prospective evaluation. For now, the most defensible conclusion is that adjuvant EGFR tyrosine kinase inhibitor use was associated with prolonged disease-free survival in this retrospective cohort.

Weighted three-year disease-free survival was 73.6% with treatment and 53.0% without treatment, while multivariable analysis produced an adjusted hazard ratio of 0.42.

Subject of Research: Retrospective evaluation of adjuvant EGFR tyrosine kinase inhibitors in resected non-small cell lung cancer with major uncommon EGFR mutations

Article Title: Adjuvant EGFR-TKI therapy in completely resected non–small cell lung cancer with major uncommon EGFR mutations: a real-world study

Article References: Yu, J., Wen, J., Chen, T., Shen, X., Xu, L., Zhao, M., Deng, J., Wu, J., Zhao, D., She, Y., & Chen, C. (2026). Adjuvant EGFR-TKI therapy in completely resected non–small cell lung cancer with major uncommon EGFR mutations: a real-world study. BMC Medicine. https://doi.org/10.1186/s12916-026-05336-3

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05336-3

Keywords: non-small cell lung cancer, EGFR mutations, adjuvant therapy, tyrosine kinase inhibitors, disease-free survival, lung cancer surgery, retrospective cohort study, molecular oncology, Adjuvant, EGFR-TKI, therapy, completely