Efficacy of gefitinib at reduced dose in EGFR mutant non-small-cell lung carcinoma.

Abstract

Background: Gefitinib is a first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that is approved by the United States Food and Drug Administration for treatment of advanced non-small-cell lung carcinoma (NSCLC) with sensitising EGFR mutations. However, gefitinib is known to have adverse effects, which may necessitate dose reduction or even change to an alternative preparation of EGFR tyrosine kinase inhibitor. The aim of the present study was to investigate whether dose reduction of gefitinib will affect the progression-free survival. Methods: This was a retrospective single-centre cohort study conducted in Queen Mary Hospital in Hong Kong that included 159 Chinese patients with advanced adenocarcinoma of the lung that carried sensitising EGFR mutations and who had received gefitinib as first-line treatment. Patients who had their gefitinib dose reduced were compared with those who were maintained on the standard dose of gefitinib. The primary endpoint was progression-free survival. Results: In all, 17 out of 159 (10.6%) patients were on reduced dose of gefitinib, 14 (82%) because of hepatotoxicity and three (18%) because of cutaneous side-effects. Patients on reduced dose and standard dose of gefitinib have comparable median progression-free survival. Hazard ratio was 1.121 (95% confidence interval [CI]=0.655-1.917, P=0.678) for the reduced dose group and 3.385 for the standard dose group (95% CI=2.181-5.255, P<0.001). Conclusions: Dose reduction in gefitinib in response to adverse effects was not associated with inferior outcome for patients on first-line gefitinib for advanced NSCLC. Dose reduction is a feasible option for patients who have significant adverse effects with gefitinib.