Low plasma concentration of gefitinib in patients with EGFR exon 21 L858R point mutations shortens progression-free survival

Abstract

Purpose

The relationship between the pharmacokinetics and effects of gefitinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) is unknown. In this study, we examined the correlation between gefitinib plasma concentration and progression-free survival (PFS) in patients with two common types of EGFR mutations: a deletion in exon 19 and point mutations in exon 21 L858R.

Methods

The retrospective analysis examined 40 patients who were administered 250 mg of gefitinib daily. All patients were diagnosed with and treated for advanced non-small cell lung carcinoma with sensitive EGFR mutations between January 2011 and November 2013 at Akita University Hospital, Akita, Japan. The 40 patients were divided into four groups by trough plasma concentration (high or low) and mutation type (exon 19 deletions or exon 21 L858R point mutations). PFS, response rate, and toxic effects were analyzed in all four groups.

Results

After excluding 5 patients, the remaining 35 were successfully analyzed. For the patients with exon 19 deletions, there was no significant difference in PFS between the high and low plasma concentration groups (median survival: 12.0 vs. 17.0 months, P = 0.9548). In contrast, the PFS was significantly shorter for patients with exon 21 point mutations and low vs. high concentrations of gefitinib (median survival: 8.0 vs. 16.0 months, P < 0.05).

Conclusions

The results suggest that low gefitinib plasma concentrations in patients with exon 21 L858R point mutations may be associated with shorter PFS in NSCLC patients.

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