Dose Reduction of EGFR-TKIs for EGFR-positive Non-small Cell Lung Cancer: A Retrospective Study.

Background/aim: The epidermal growth factor receptor (EGFR) gene was the first driver gene discovered in non-small cell lung cancer (NSCLC), and the introduction of tyrosine kinase inhibitors (TKIs) has improved patient prognosis, but often at reduced doses. Conventional dose determination methods for cytotoxic antitumor drugs were not applicable to EGFR-TKIs and were determined differently. The purpose of this study was to determine the characteristics of patients undergoing EGFR-TKI dose reduction, and the impact of such dose reduction on survival.

Patients and methods: Patient characteristics, treatment, overall survival, and progression-free survival of patients with EGFR mutation-positive NSCLC treated with EGFR-TKIs between August 2008 and April 2024 at two hospitals were retrospectively evaluated.

Results: Of 165 patients, 67.3% received TKI dose reduction; patients who received TKI dose reduction had a smaller body surface area (p=0.029), which was more common in patients with better performance status (p=0.026). Side effects, especially diarrhea and rash, were the main reasons for this. Overall survival was significantly longer in the dose reduction group than in the recommended dose group (p=0.011). Multivariate analysis showed that TKI dose reduction was a favorable factor with a hazard ratio of 0.68 (p=0.046).

Conclusion: Reducing TKI dose is an option for patients with EGFR-mutated NSCLC, especially in elderly or underweight patients who develop adverse effects, and there is no reason to hesitate to reduce the TKI dose in these patients.