PO.ET09.05 · 实验与分子治疗
PI3K抑制剂致高级别高血糖的风险——一项meta分析
The risk of high-grade hyperglycemia with PI3K inhibitors-a meta-analysis
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摘要 Abstract
中文摘要
背景：磷酸肌醇3激酶（PI3K）抑制剂是一类有前景的癌症治疗药物，但其临床应用受到毒性（尤其是高级别高血糖）的限制。目前，接受PI3K抑制剂治疗的患者发生高血糖的总体风险尚未得到充分了解。我们基于当前可获得的已发表随机对照试验（RCT）数据，对接受PI3K抑制剂治疗患者的高级别高血糖风险进行了meta分析。
方法：开展了一项系统性meta分析，纳入评价PI3K抑制剂用于癌症患者的II-III期RCT。主要终点为≥3级高血糖的发生率和相对风险。根据纳入研究的异质性，使用随机效应或固定效应模型计算合并效应量。
结果：共纳入16项符合条件的RCT中的4977例患者进行分析。高级别高血糖的总体发生率为12.7%（637/4977）。与对照相比，PI3K抑制与高级别高血糖风险的显著增加相关（RR：2.27；95% CI，1.74-2.80；p<0.001），异质性中等（I²=38.9%）。亚组分析显示，对照类型显著调节毒性风险（p<0.001），在使用安慰剂对照的试验中观察到最大风险（RR：2.60；95% CI，2.05-3.15），其次为活性药物对照（RR：1.50；95% CI，0.49-2.52）。PI3K抑制剂亚型也调节风险（p<0.001）。PI3K-alpha选择性抑制剂与最高风险相关（RR：3.80；95% CI，2.50-5.11），其次为泛PI3K抑制剂（RR：2.15；95% CI，1.79-2.52）和PI3K/mTOR双重抑制剂（RR：1.46；95% CI，0.61-2.31）。I类alpha/beta/delta抑制剂未显示出显著升高。
结论：PI3K抑制剂显著增加≥3级高血糖的风险，其异质性由对照类型和抑制剂亚型驱动。PI3K-alpha选择性药物风险显著升高，凸显了在临床应用中进行严密代谢监测和量身定制管理策略的必要性。
查看英文原文 English abstract
Background: Phosphoinositide 3-kinase (PI3K) inhibitors are a promising therapeutic class in cancer treatment and their clinical utility has been limited by toxicity, particularly high-grade hyperglycemia. Currently the overall risk of hyperglycemia in patients treated with PI3K inhibitors has not been well understood. We performed a meta-analysis on the risk of high-grade hyperglycemia in patients treated with PI3K inhibitors based on currently available published randomized control trial (RCT) data.
Methods: A systematic meta-analysis was conducted including phase II-III RCTs evaluating PI3K inhibitors in cancer patients. The primary endpoints were the incidence and relative risk of grade ≥3 hyperglycemia. Pooled effect sizes were calculated using random- or fixed-effects models based on the heterogeneity of included studies.
Results: A total of 4977 patients across 16 eligible RCTs were included for analysis. The overall incidence of high-grade hyperglycemia was 12.7% (637/4977). Compared to controls, PI3K inhibition was associated with a significantly increased risk of high-grade hyperglycemia (RR: 2.27; 95% CI, 1.74-2.80; p < 0.001), with moderate heterogeneity (I² = 38.9%). Subgroup analyses revealed that control type significantly moderated toxicity risk (p < 0.001), with the greatest risk observed in trials with placebo controls (RR: 2.60; 95% CI, 2.05-3.15) and active controls (RR:1.50; 95% CI, 0.49-2.52). PI3K inhibitor subtype also moderated risk (p < 0.001). PI3K-alpha selective inhibitors were associated with the highest risk (RR: 3.80; 95% CI, 2.50-5.11), followed by pan-PI3K (RR: 2.15; 95% CI, 1.79-2.52) and PI3K/mTOR dual inhibitors (RR:1.46; 95% CI, 0.61-2.31). Class I alpha/beta/delta inhibitors showed no significant elevation.
Conclusions: PI3K inhibitors substantially increased the risk of grade ≥3 hyperglycemia, with heterogeneity driven by control type and inhibitor subtype. The markedly elevated risk with PI3K-alpha selective agents highlights the need for vigilant metabolic monitoring and tailored management strategies in clinical use.
利益披露 Disclosure
Z. Rong, None..
S. Wu, None.