Background:: Phosphatidylinositol 3-kinase (PI3K) inhibitors belong to the class of drugs that inhibit the activity of the PI3K protein, which is commonly overexpressed in breast cancer cells. However, there is a need to summarize the evidence to provide conclusive advice on the benefit of PI3K inhibitors in breast cancer patients. Therefore, this review assessed the effectiveness and safety of the PI3K inhibitors amongst breast cancer patients. Methods:: Searches were made in PubMed Central, EMBASE, MEDLINE, SCOPUS, CENTRAL, WHO trial registry and Clinicaltrials.gov up to December 2022. Meta-analysis was executed using the random-effects model. Pooled hazard ratio (HR)/risk ratio (RR) was reported with 95% confidence intervals (CIs). Results:: In total, 13 studies were included in the analysis. Most were multi-country studies and had a higher risk of bias. Regarding the efficacy parameters, pooled HR for progression-free survival was 0.79 (95%CI: 0.67-0.92), pooled RR for complete response was 1.54 [95%CI: 1.14 to 2.09], partial response was 1.18 [95%CI: 0.87-1.61], overall response was 1.20 [95%CI: 0.93-1.56], stable disease was 1.09 [95%CI: 0.78-1.53], progressive disease was 0.80 [95%CI: 0.74 to 0.87], and clinical benefit was 1.08 [95%CI: 0.80-1.49]. For safety parameters, pooled RR for hyperglycemia was 4.57 [95%CI: 3.15-6.62], and gastrointestinal toxicity was 1.82 [95%CI: 1.56 to 2.14]. Conclusion:: PI3K inhibitors had better efficacy than the present standard of concern for patients with breast cancer, especially among patients with PIK3CA mutations. Hence, clinicians and oncologists can provide this drug for the target population with extra caution for diabetes patients.

中文翻译：

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磷脂酰肌醇 3-激酶抑制剂对乳腺癌患者的疗效和安全性：随机对照试验的系统评价和荟萃分析

背景：磷脂酰肌醇 3 激酶 (PI3K) 抑制剂属于抑制 PI3K 蛋白活性的药物，PI3K 蛋白通常在乳腺癌细胞中过度表达。然而，需要总结证据，以就 PI3K 抑制剂对乳腺癌患者的益处提供结论性建议。因此，本综述评估了 PI3K 抑制剂在乳腺癌患者中的有效性和安全性。方法：：在 PubMed Central、EMBASE、MEDLINE、SCOPUS、CENTRAL、WHO 试验注册中心和 ClinicalTrials.gov 中进行检索，截至 2022 年 12 月。使用随机效应模型进行荟萃分析。汇总风险比 (HR)/风险比 (RR) 报告的置信区间 (CI) 为 95%。结果：：分析中总共纳入了 13 项研究。大多数是多国研究，并且存在较高的偏倚风险。关于疗效参数，无进展生存期的汇总 HR 为 0.79（95% CI：0.67-0.92），完全缓解的汇总 RR 为 1.54 [95% CI：1.14 至 2.09]，部分缓解为 1.18 [95% CI： 0.87-1.61]，总体缓解率为 1.20 [95%CI：0.93-1.56]，疾病稳定为 1.09 [95%CI：0.78-1.53​​]，疾病进展为 0.80 [95%CI：0.74 至 0.87]，临床获益为 1.08 [95% CI: 0.80-1.49]。对于安全性参数，高血糖的汇总 RR 为 4.57 [95% CI：3.15-6.62]，胃肠道毒性为 1.82 [95% CI：1.56 至 2.14]。结论:: PI3K 抑制剂对乳腺癌患者，尤其是 PIK3CA 突变患者的疗效优于目前关注的标准。因此，临床医生和肿瘤学家可以为目标人群提供这种药物，但对糖尿病患者要格外小心。