Impact of first-line <i>EGFR</i> TKI dose reduction on survival and treatment sequencing in metastatic <i>EGFR</i> -mutant non–small cell lung cancer: A real-world cohort study.

Abstract

e20746 Background: Dose reduction during first-line EGFR tyrosine kinase inhibitor (TKI) therapy is common in metastatic EGFR -mutant non–small cell lung cancer (NSCLC), particularly in older patients and those experiencing toxicity. However, the oncologic consequences of dose modification including its effect on survival, treatment durability, and ability to receive subsequent therapy remain unclear. We evaluated the association between first-line EGFR TKI dose reduction and clinical outcomes in a real-world cohort. Methods: We conducted a retrospective cohort study of patients with EGFR -mutated metastatic NSCLC treated with first-line EG FR TKI therapy. Primary endpoints were progression-free survival (PFS) and overall survival (OS), measured from initiation of first-line therapy. Secondary endpoints included time to treatment discontinuation (TTD) and receipt of second-line (2L) systemic therapy. Dose reduction were analyzed as binary characteristics. Survival outcomes were estimated using Kaplan–Meier methods and multivariable Cox regression. Receipt of 2L therapy was evaluated using logistic regression among patients who discontinued first-line therapy. Models were adjusted for age, ECOG performance status (PS), and EGFR TKI type. Results: Among 112 patients, median age was 70 years, and 36% were aged ≥75 years. First-line EGFR TKIs included osimertinib (57%), erlotinib (30%), and afatinib (13%). Dose reduction was more frequent among patients aged ≥75 years compared with those &lt; 75 years (32% vs 10%, p = 0.01). In multivariable Cox models adjusting for age, PS, and TKI generation, first-line EGFR TKI dose reduction was not associated with worse overall survival (HR 1.86, 95% CI 0.72-4.77), progression-free survival (HR 1.45, 95% CI 0.68-1.90), or time to treatment discontinuation (HR 1.47, 95% CI 0.74-2.8). Among patients who discontinued first-line EGFR TKI therapy, dose reduction was also not associated with lower odds of receiving second-line treatment (OR 0.13, 95% CI 0.01-1.07). In contrast, ECOG ≥2 remained independently associated with worse outcomes across endpoints, while age ≥75 was not prognostic. Conclusions: In this real-world EGFR -mutant NSCLC cohort, first-line EGFR TKI dose reduction was not associated with inferior survival, reduced treatment durability, or diminished access to subsequent therapy. Performance status, not age or dose modification, was the dominant predictor of outcomes. These findings support individualized dose adjustments during EGFR TKI therapy when clinically indicated, without concern for compromising oncologic efficacy or future treatment opportunities.