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Purpose <p>The inflammatory cytokine interleukin (IL)-6 reduces the activity of drug metabolic enzymes and promotes tumor progression. We investigated the effect of IL-6 on the pharmacokinetics of osimertinib and the association between an <i>IL-6</i> polymorphism and clinical outcomes in 30 patients with non-small cell lung cancer (NSCLC).</p> Methods <p>Osimertinib and IL-6 plasma concentrations were measured on day 15 after therapy initiation. The genotype of <i>IL-6</i> 1800796G &gt; C was identified using polymerase chain reaction–restriction fragment length polymorphism. Risk factors affecting overall survival (OS) were assessed by Cox proportional hazard regression analysis.</p> Results <p>The IL-6 concentration was significantly correlated with the osimertinib trough plasma concentration (<i>r</i> = 0.423, <i>P</i> = 0.020) and area under the plasma concentration–time curve (<i>r</i> = 0.420, <i>P</i> = 0.021). The IL-6 concentration was significantly higher in patients with the <i>IL-6</i> rs1800796G allele versus C/C genotype (<i>P</i> = 0.024). OS was significantly shorter in patients with the <i>IL-6</i> rs1800796G allele versus C/C genotype (median: 15.1 vs. 48.9 months, <i>P</i> = 0.005). Univariate and multivariate analyses indicated that the <i>IL-6</i> rs1800796G allele is an independent risk factor for OS (crude hazard ratio = 7.07; <i>P</i> = 0.014; adjusted hazard ratio = 6.38; <i>P</i> = 0.021).</p> Conclusion <p>A higher IL-6 concentration was associated with reduced metabolic activity of osimertinib, leading to increased osimertinib exposure. As the IL-6 concentration was higher in NSCLC patients with the <i>IL-6</i> rs1800796G allele, it might be an independent prognostic factor for patients treated with osimertinib.</p>

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Influence of interleukin-6 on the pharmacokinetics and pharmacodynamics of osimertinib in patients with non-small cell lung cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月29日

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  • Hayato Yokota,
  • Kazuhiro Sato,
  • Sho Sakamoto,
  • Yuji Okuda,
  • Masahide Takeda,
  • Yumiko Akamine,
  • Katsutoshi Nakayama,
  • Masatomo Miura

摘要

Purpose

The inflammatory cytokine interleukin (IL)-6 reduces the activity of drug metabolic enzymes and promotes tumor progression. We investigated the effect of IL-6 on the pharmacokinetics of osimertinib and the association between an IL-6 polymorphism and clinical outcomes in 30 patients with non-small cell lung cancer (NSCLC).

Methods

Osimertinib and IL-6 plasma concentrations were measured on day 15 after therapy initiation. The genotype of IL-6 1800796G > C was identified using polymerase chain reaction–restriction fragment length polymorphism. Risk factors affecting overall survival (OS) were assessed by Cox proportional hazard regression analysis.

Results

The IL-6 concentration was significantly correlated with the osimertinib trough plasma concentration (r = 0.423, P = 0.020) and area under the plasma concentration–time curve (r = 0.420, P = 0.021). The IL-6 concentration was significantly higher in patients with the IL-6 rs1800796G allele versus C/C genotype (P = 0.024). OS was significantly shorter in patients with the IL-6 rs1800796G allele versus C/C genotype (median: 15.1 vs. 48.9 months, P = 0.005). Univariate and multivariate analyses indicated that the IL-6 rs1800796G allele is an independent risk factor for OS (crude hazard ratio = 7.07; P = 0.014; adjusted hazard ratio = 6.38; P = 0.021).

Conclusion

A higher IL-6 concentration was associated with reduced metabolic activity of osimertinib, leading to increased osimertinib exposure. As the IL-6 concentration was higher in NSCLC patients with the IL-6 rs1800796G allele, it might be an independent prognostic factor for patients treated with osimertinib.