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Effects of STAT3 polymorphisms and pharmacokinetics on the clinical outcomes of gefitinib treatment in patients with EGFR‐mutation positive non‐small cell lung cancer
Author(s) -
Yokota Hayato,
Sato Kazuhiro,
Sakamoto Sho,
Okuda Yuji,
Asano Mariko,
Takeda Masahide,
Nakayama Katsutoshi,
Miura Masatomo
Publication year - 2020
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.13173
Subject(s) - gefitinib , medicine , lung cancer , confidence interval , pharmacokinetics , oncology , gastroenterology , pharmacology , cancer , epidermal growth factor receptor
What is known and objective We investigated the correlations among signal transducer and activator of transcription 3 ( STAT3 ) rs4796793C >G polymorphism, gefitinib pharmacokinetics and clinical responses in Japanese patients with non‐small cell lung cancer receiving gefitinib therapy. Methods Forty‐five patients were enrolled in this study. Plasma trough concentrations (C 0 ) of gefitinib at the steady‐state were measured by high‐performance liquid chromatography. Results and discussion Patients having a gefitinib C 0 of at least ≥200 ng/mL had significantly longer PFS than patients having a C 0 of <200 ng/mL (median [95% confidence interval (CI)] PFS: 11.0 [8.2‐13.7] and 5.3 [0.0‐12.0] months, respectively, P = .042). There were no significant differences in PFS between patients with STAT3 rs4796793C/C and G alleles; however, patients with STAT3 rs4796793C/C having a gefitinib C 0 of ≥ 200 ng/mL had significantly longer progression‐free survival (PFS) and overall survival (OS) than those with a C 0 of <200 ng/mL (median [95% CI] PFS: 11.4 [4.1‐18.6] and 3.0 [0.0‐7.0] months, respectively, P = .008; median [95% CI] OS: 20.6 [7.4‐33.7] and 12.6 [10.1‐15.1] months, respectively, P = .042). In patients with the STAT3 rs4796793G allele, there were no significant differences in PFS and OS between the two gefitinib C 0 groups. In addition, there were no significant differences in PFS or OS according to smoking, presence of proton pump inhibitor combination, or onset of side effects. What is new and conclusion Clinical outcomes of gefitinib in patients with the STAT3 rs4796793C/C genotype depended on plasma concentrations of gefitinib. In addition to information regarding EGFR mutations, the STAT3 rs4796793C >G polymorphism and gefitinib C 0 may be potential predictors of clinical outcomes after beginning of gefitinib therapy.