Association Between Osimertinib Dose Reduction and Treatment Outcomes in First-Line EGFR-Mutated Advanced NSCLC: The Impact of Post-Progression Management.

Abstract

Background: Osimertinib is the standard first-line treatment for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). However, the impact of dose-reduction on survival and the role of post-progression management in real-world settings remain unclear.

Methods: We conducted a multi-institutional retrospective cohort study on patients with EGFR-mutated advanced NSCLC who received first-line osimertinib between January 2018 and December 2023. Patients were classified into dose-reduced and full-dose groups. Primary endpoints were time to treatment failure (TTF) and overall survival (OS). The subsequent treatment after progression was also exploratively assessed to evaluate the impact of initial dose modification on the entire treatment sequence.

Results: A total of 90 patients were analyzed, consisting of 61 patients in the full-dose group and 29 in the dose-reduction group. Median follow-up was 21.5 months (IQR 9.1-37.2). The dose-reduced group had significantly worse baseline performance status (PS) (PS 2-3: 37.9% vs. 14.8%, p = 0.014). Despite this, dose reduction showed no significant impact on TTF (adjusted HR 0.66, 95% CI 0.40-1.10, p = 0.11) or OS (HR 0.97, 95% CI 0.59-1.58, p = 0.89). Multivariate analysis revealed that transition to best supportive care (BSC) after progression, rather than initial dose reduction, was associated with OS (hazard ratio, 7.40; p < 0.0001). The proportions of patients receiving subsequent chemotherapy were comparable between the groups.

Conclusions: Osimertinib dose reduction in the first-line setting was not associated with inferior OS, suggesting that appropriate dose modification helps maintain PS. Transition to BSC after progression, rather than initial dose intensity, was associated with poor prognosis.