Presentation (CTI)

OBJECTIVES: EGFR-TKIs are standard first-line therapies for advanced NSCLC, yet treatment-emergent interstitial lung disease (ILD) often necessitates treatment interruption. Following recovery, clinicians face a dilemma between TKI rechallenge and switching to chemotherapy. Current evidence is largely restricted to small-scale, retrospective studies, highlighting a critical gap in large-scale, population-based real-world evidence regarding the optimal subsequent strategy. We conducted a retrospective cohort study to compare the safety and effectiveness of EGFR-TKI rechallenge versus chemotherapy in patients with advanced NSCLC who experienced ILD during first-line EGFR-TKIs treatment.
METHODS: Using the Taiwan National Health Insurance Research Database (NHIRD), we identified patients with advanced NSCLC between 2011 and 2020 whose first-line therapy (gefitinib, erlotinib, or afatinib) was interrupted by ILD. Based on their subsequent treatment, patients were categorized into the 'rechallenge' cohort (re-administration of an EGFR-TKI) or the 'non-rechallenge' cohort (switch to chemotherapy). Stabilized inverse probability treatment weighting (SIPTW) was used to balance covariates. Primary outcomes were ILD recurrence, treatment failure, and overall survival (OS), analyzed using weighted Cox regression models to estimate hazard ratios (HRs) and the Fine-Gray sub-distribution hazard model to address the competing risk of death.
RESULTS: In the preliminary analysis of nearly 800 SIPTW-weighted patients, EGFR-TKI rechallenge was not associated with a significantly higher risk of ILD recurrence (sHR 1.36, p > 0.05) or treatment failure (sHR 1.00, p > 0.05) compared to chemotherapy. Notably, the 'rechallenge' cohort achieved a statistically significant survival advantage in OS compared to the chemotherapy group (weighted log-rank p < 0.05).
CONCLUSIONS: EGFR-TKI rechallenge is a feasible and effective strategy for advanced NSCLC patients who have recovered from initial EGFR-TKI-associated ILD. Rechallenge offers a significant survival benefit without a marked increase in ILD recurrence risk compared to chemotherapy. These findings provide robust real-world evidence to support clinical decision-making and insurance reimbursement considerations for this challenging patient population.