Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Biomed Res Int. 2020 Dec 3;2020:7451576. doi: 10.1155/2020/7451576. eCollection 2020.
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a promising treatment target for patients with breast cancer (BC). Our study aimed to evaluate the most effective and safe PI3K inhibitor for patients with BC, especially in PIK3CA mutation.
Electronics databases were systematically searched from their inception to June 2020 for published randomized controlled trials (RCTs) comparing PI3K inhibitor therapy versus non-PI3K inhibitor therapy in patients with BC that mentioned or reported data of PIK3CA-mutated patient subgroups. Eligible RCTs had to report at least one of the following clinical outcomes: objective response rate (ORR), progression-free survival (PFS), or adverse events (AE).
Nine eligible RCTs involving 3872 BC patients and four PI3K inhibitor therapy arms (i.e., alpelisib, buparlisib, pictilisib, and taselisib) were included. In evaluating ORR, beneficial significant results of PI3K inhibitors could be found in the PIK3CA mutated group (1.952, 1.012 to 3.766); analogous results could also be found in 6m-PFS (1.519, 1.144 to 2.018) and PFS from HR data (-0.346, -0.525 to -0.168). From pairwise and network meta-analyses, buparlisib showed the most favorable ORR, as it was significantly different from fulvestrant in the PIK3CA-mutated patient group (2.80, 1.56 to 5.03). Alpelisib ranked first in the assessment of 6m-PFS and was significantly different from fulvestrant in the PIK3CA-mutated group (2.33, 1.45 to 3.44). The above PI3K inhibitors had good safety with few serious AEs. PROSPERO registration CRD42020193932.
The PI3K inhibitors alpelisib and buparlisib appear to have superior efficacy and safety therapeutic choices for patients with BC, especially in PIK3CA-mutated patients.
磷脂酰肌醇 3-激酶（PI3K）信号通路是治疗乳腺癌（BC）患者的有前途的治疗靶点。我们的研究旨在评估对 BC 患者最有效和安全的 PI3K 抑制剂，特别是在 PIK3CA 突变的情况下。
系统地从电子数据库中搜索从成立到 2020 年 6 月发表的比较 PI3K 抑制剂治疗与非 PI3K 抑制剂治疗 BC 患者的随机对照试验（RCT），这些试验提到或报告了 PIK3CA 突变患者亚组的数据。合格的 RCT 必须报告以下至少一种临床结果：客观缓解率（ORR）、无进展生存期（PFS）或不良事件（AE）。
纳入了 9 项合格的 RCT，涉及 3872 名 BC 患者和 4 种 PI3K 抑制剂治疗组（即 alpelisib、buparlisib、pictilisib 和 taselisib）。在评估 ORR 时，PI3K 抑制剂在 PIK3CA 突变组中显示出有益的显著结果（1.952，1.012 至 3.766）；在 6m-PFS（1.519，1.144 至 2.018）和 HR 数据的 PFS 中也可以得到类似的结果（-0.346，-0.525 至-0.168）。从成对和网络荟萃分析来看，buparlisib 的 ORR 最为有利，因为它在 PIK3CA 突变患者组中与氟维司群的差异有统计学意义（2.80，1.56 至 5.03）。Alpelisib 在评估 6m-PFS 方面排名第一，在 PIK3CA 突变组中与氟维司群的差异有统计学意义（2.33，1.45 至 3.44）。这些 PI3K 抑制剂具有良好的安全性，很少有严重的不良事件。PROSPERO 注册 CRD42020193932。
PI3K 抑制剂 alpelisib 和 buparlisib 似乎对 BC 患者，特别是 PIK3CA 突变患者具有更好的疗效和安全性治疗选择。
