Clinical Impact of Osimertinib Dose Reduction in the First-Line Setting on EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Retrospective Monocentric Study.

Purpose: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. In the FLAURA trial, osimertinib demonstrated longer progression-free survival (PFS) and overall survival (OS) compared to gefitinib or erlotinib. In the trial, dose reductions occurred in 5% of patients, primarily due to QT prolongation. However, various adverse events can also lead to dose reductions in clinical practice, and the efficacy of osimertinib after dose reduction remains unclear. The present study was conducted to evaluate the clinical impact of osimertinib dose reduction.

Patients and methods: This monocentric retrospective study was conducted at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital. Ninety patients with EGFR mutation-positive non-squamous non-small-cell lung cancer receiving osimertinib as their first-line therapy between August 2018 and December 2021 were included.

Results: Of the cohort, 23 patients had an osimertinib dose reduction during their clinical course. The dose reduction group tended to have a lower median body weight and a higher proportion of elderly patients aged 80 years or older. The median PFS was 21.2 months (95% confidence interval [CI]: 8.22-34.18) in the dose reduction group and 18.6 (95% CI: 13.04-24.23) months in the regular-dose group. The median OS was 29.6 months (95% CI: 17.44-41.70) in the osimertinib dose-reduction group and 37.7 (95% CI: 27.10-48.23) months in the regular-dose group. Dose reduction did not significantly impact the time-dependent hazard ratio (HR) for PFS (HR 1.22 [95% CI: 0.55-1.89]) or OS (HR: 1.24 [95% CI: 0.64-2.42]). The adverse events leading to dose reduction were mainly rash, anorexia, and paronychia, and no fatal adverse events were observed after dose reduction.

Conclusion: The present study suggests that dose reduction may not compromise the efficacy of osimertinib. However, the clinical impact of dose reduction is not fully understood. Physicians should carefully weigh its benefits and risks before implementation.