Tanda Masaaki, Yamamoto Kazuhiro, Hori Tomoki, Nishiguchi Hiroki, Yagi Miki, Shimizu Michiko, Konishi Toru, Ozaki Tomonori, Yoshioka Natsue, Tachihara Motoko, Ito Takefumi, Ikushima Shigeki, Omura Tomohiro, Yano Ikuko
Department of Pharmacy, Kobe University Hospital, Kobe, Japan.
Department of Pharmacy, Kobe University Hospital, Kobe, Japan;
Anticancer Res. 2023 Apr;43(4):1775-1783. doi: 10.21873/anticanres.16331.
BACKGROUND/AIM: Osimertinib is a key drug for treating epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Genetic differences may be associated to adverse events (AEs) induced by osimertinib. This retrospective observational multicenter study evaluated the association of genotypes, including STAT3 -1697C>G, CYP3A5 6986A>G, and ABCG2 421C>A, with the incidence of osimertinib-induced AEs in patients with EGFR mutation-positive NSCLC.
A total of 85 patients treated with osimertinib (Institution A: 33 patients, Institution B: 52 patients) were enrolled in the study. Single nucleotide polymorphisms were determined by real-time PCR, and the incidence of AEs was compared for each genotype.
Paronychia incidence was 59% for the CC genotype, 19% for the CG genotype, and 19% for the GG genotype at STAT3 -1697C>G. A genotype-related trend was observed (Cochran-Armitage test, p=0.009). Multivariate analysis showed that the CC genotype at STAT3 -1697C>G and female sex were significant independent factors associated with paronychia [odds ratio (OR)=6.41, 95% confidence interval (CI)=1.94-21.20 and OR=3.40, 95%CI=1.03-11.22, respectively]. The incidence of diarrhea was 53% for the CC genotype, 30% for the AC genotype, and 29% for the AA genotype at ABCG2 421C>A, and a genotype-related trend was observed (p=0.048). However, the CC genotype at ABCG2 421C>A was not a significant independent factor associated with diarrhea in multivariate analysis. No significant associations were detected between other polymorphisms and the incidence of AEs.
STAT3 -1697C>G may be a novel risk factor for osimertinib-induced paronychia in patients with NSCLC.
背景/目的：奥希替尼是治疗表皮生长因子受体（EGFR）突变阳性非小细胞肺癌（NSCLC）的关键药物。基因差异可能与奥希替尼诱导的不良事件（AE）相关。这项回顾性观察性多中心研究评估了基因型（包括STAT3 -1697C>G、CYP3A5 6986A>G和ABCG2 421C>A）与EGFR突变阳性NSCLC患者中奥希替尼诱导的AE发生率之间的关联。
共有85例接受奥希替尼治疗的患者（机构A：33例患者，机构B：52例患者）纳入研究。通过实时聚合酶链反应测定单核苷酸多态性，并比较每种基因型的AE发生率。
在STAT3 -1697C>G位点，甲沟炎发生率在CC基因型为59%，CG基因型为19%，GG基因型为19%。观察到基因型相关趋势（ Cochr an-Armitage检验，p = 0.009）。多变量分析显示，STAT3 -1697C>G位点的CC基因型和女性是与甲沟炎相关的显著独立因素[比值比（OR）=6.41，95%置信区间（CI）=1.94 - 21.20；OR = 3.40，95%CI = 1.03 - 11.22]。在ABCG2 421C>A位点，腹泻发生率在CC基因型为53%，AC基因型为30%，AA基因型为29%，观察到基因型相关趋势（p = 0.048）。然而，在多变量分析中，ABCG2 421C>A位点的CC基因型不是与腹泻相关联的显著独立因素。未检测到其他多态性与AE发生率之间的显著关联。
STAT3 -1697C>G可能是NSCLC患者中奥希替尼诱导甲沟炎的一个新的危险因素。
