ArticleScientific reports2026
Optimal treatment strategies for EGFR mutant advanced lung adenocarcinoma patients with targeted therapy resistance and correlation analysis of PD-L1 expression with ICI efficacy.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Third-generation tyrosine kinase inhibitors (TKIs) have become the standard treatment for advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma. Currently, after developing resistance to third-generation EGFR-TKIs, treatment regimens based on platinum-based dual-agent chemotherapy yield limited clinical benefit. This retrospective study analyzed patients who progressed on first-line third-generation EGFR-TKIs between March 2019 and September 2024 and received second-line chemotherapy-based regimens. Patients were further stratified based on PD-L1 expression status and immune checkpoint inhibitor (ICI) use to assess the correlation between PD-L1 expression and ICI efficacy. Among 107 patients who progressed on third-generation TKIs as first-line therapy, 35 received chemotherapy (C), 29 received chemotherapy combined with anti-angiogenic (C + A), 22 received chemoimmunotherapy (C + I), and 21 received chemoimmunotherapy combined with anti-angiogenic therapy (C + I + A). Second-line median progression-free survival (mPFS2) were 4.89 months, 6.74 months, 7.80 months, and 8.00 months, respectively. Non-ICIs group vs. ICIs group: mPFS2 was 5.06 months vs. 8.00 months, P = 0.031. In PD-L1-negative, positive, and strong subgroups, the Non-ICIs group vs. ICIs group showed mPFS2 of 5.32 months vs. 6.68 months, P = 0.724; 4.89 months vs. 8.63 months, P = 0.009, and 3.11 months vs. 13.52 months, P < 0.001. Among patients with EGFR-TKI resistance, combination immunochemotherapy with or without anti-angiogenic therapy demonstrates distinct advantages over chemotherapy alone. Adding ICIs in PD-L1-positive patients improves progression-free survival, with greater clinical benefit observed at higher PD-L1 expression levels. Within the immunotherapy cohort, PD-L1-high patients show a trend toward more pronounced benefit from ICIs.
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