Efficacy of immunotherapy-based regimens in Russian patients with <i>EGFR</i> -mutated metastatic NSCLC after EGFR TKI failure: A multi-institution real-world analysis.

e20628 Background: Patients with EGFR-mutated (EGFRm) metastatic non-small cell lung cancer (mNSCLC) generally derive limited benefit from immune checkpoint inhibitors (ICIs), yet outcomes may vary across clinical and molecular subgroups. We evaluated real-world outcomes of ICI-based therapy versus chemotherapy with/without bevacizumab after EGFR TKI progression in a Russian cohort. Methods: Multi-institution retrospective analysis (2019–2025) of EGFRm mNSCLC patients after EGFR TKI progression treated with subsequent systemic therapy. Regimens were categorized as chemotherapy ± bevacizumab (CT±B) or ICI-based therapy (ICI+CT±B). Progression Free Survival (PFS) was measured from start of the subsequent line to progression or death. Analyses were exploratory and unadjusted for confounding; subgroup analyses included EGFR genotype, T790M , PD-L1 expression, and ECOG. Results: A total of 258 patients were included; 70.6% were female. Median age was 62 years (range 28–87); 68% were never-smokers. EGFR variants included ex19del (59.2%), L858R (35.0%), and rare mutations (7.8%). T790M testing was performed in 24.6% of patients and was positive in 42.8% of those tested. Subsequent therapy consisted of CT±B in 68% and ICI-based therapy in 32%. Overall, mPFS favored ICI-based therapy versus CT±B (6.7 vs 4.7 months; p = 0.03) and versus CT+B (6.7 vs 5.5 months; p = 0.043). By genotype, mPFS favored ICI-based therapy in L858R (8.3 vs 5.2 months; p = 0.044) and showed a trend in rare mutations (6.8 vs 3.9 months; p = 0.064), but not in ex19del (5.9 vs 4.5 months; p = 0.27). By T790M status, no difference was observed in T790M+ disease (4.4 vs 4.2 months; p = 0.326), whereas mPFS was longer with ICI-based therapy in T790M− disease (7.0 vs 4.8 months; p = 0.02). The PFS benefit with ICI-based therapy was more statistically pronounced in PD-L1 ≥1% compared with PD-L1 = 0%, and did not vary by ECOG status. Conclusions: In our Russian real-world EGFRm mNSCLC cohort after EGFR TKI failure ICI-based regimens were associated with longer PFS compared with CT±B, with the most pronounced benefit in L858R and possibly rare EGFR mutations, limited or no benefit in ex19del and T790M+ disease, and stronger signal in PD-L1 ≥1%. Findings are exploratory and warrant validation in confounding-adjusted analyses and prospective studies.