Real-world survival outcomes of immune checkpoint inhibitor therapy after standard treatment failure in EGFR-mutated NSCLC: A nationwide cohort study

Abstract

Background

Immune checkpoint inhibitors (ICIs) have shown limited efficacy in EGFR-mutated NSCLC, and their role in later-line settings remains unclear. This study aimed to evaluate the real-world effectiveness of ICI monotherapy compared to chemotherapy in patients with EGFR-mutated NSCLC who had limited remaining treatment options.

Methods

We conducted a target trial emulation using data from the Cancer Public Library Database under the K-CURE project, which integrates national cancer registry, mortality, medical check-up and health insurance claims data in Korea. Eligible patients were aged ≥ 18 years, had EGFR-mutated NSCLC with progression after both EGFR-TKI and platinum-based chemotherapy, and initiated ICI monotherapy or chemotherapy between August 2017 and December 2020. Propensity score matching was used to balance treatment groups. Overall survival was analyzed using time-dependent statistical methods to account for non-proportional hazards.

Results

Of 1,914 eligible patients, 663 matched pairs were analyzed. While standard Cox analysis showed no significant OS difference (HR 0.91, 95 % CI 0.80–1.03), time-dependent analyses revealed a late survival benefit for ICI beyond 6.8 months (HR 0.72, 95 % CI 0.59–0.88). Subgroup analyses revealed heterogeneous treatment effects, with greater long-term benefits in patients of older age, those with concurrent malignancies, and those without prior osimertinib exposure. Sensitivity analyses suggested a potential role for high PD-L1 expression as a biomarker of ICI response in this setting.

Conclusion

ICI monotherapy may offer time-dependent survival benefits over chemotherapy in selected patients with EGFR-mutated NSCLC after standard treatment failure, supporting its consideration in later-line clinical decision-making.