Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.
Liaoning Key Laboratory of Molecular Targeted anti-tumor Drug Development and Evaluation; Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, China Medical University, Shenyang, Liaoning, China.
Expert Rev Clin Pharmacol. 2023 Mar;16(3):245-256. doi: 10.1080/17512433.2023.2188193. Epub 2023 Mar 9.
Poly-ADP-ribose polymerase inhibitors (PARPis) have emerged as a new class of therapeutic agents for breast cancer patients with breast cancer susceptibility gene () mutations. However, the efficacy and toxicity of PARPis have not been clearly established.
This study comprehensively evaluated the efficacy and safety of PARPis in patients with BRCA-mutated breast cancer. Online databases were systematically searched, and six clinical trials were included. The primary endpoint of efficacy was progression-free survival (PFS), whereas the secondary endpoints were overall survival (OS) and objective response rate (ORR). Additionally, we assessed the safety of PARPis.
The results of the meta-analysis showed that PARPis can effectively improve the PFS and OS in patients compared with the control group. The pooled HR (PARPi vs control groups) was 0.63 (95% CI, 0.55 - 0.73) and 0.83 (95% CI, 0.73 to -0.95) for PFS and OS, respectively. In safety, PARPis demonstrated controllable adverse reactions. There were no significant differences in overall AEs or grade ≥3 AEs between the PARP inhibitor and control arms.
Our results confirm the efficacy and safety of PARPis in patients with BRCA-mutated breast cancer, and more specifically clarify the efficacy of PARPis alone or in combination with other chemotherapy drugs. [Figure: see text].
聚 ADP-核糖聚合酶抑制剂 (PARPi) 已成为乳腺癌易感基因 () 突变的乳腺癌患者的一类新的治疗药物。然而,PARPi 的疗效和毒性尚未明确。
本研究全面评估了 PARPi 在 BRCA 突变型乳腺癌患者中的疗效和安全性。系统地在线数据库搜索,并纳入了 6 项临床试验。疗效的主要终点是无进展生存期 (PFS),次要终点是总生存期 (OS) 和客观缓解率 (ORR)。此外,我们评估了 PARPi 的安全性。
荟萃分析的结果表明,PARPi 可有效提高患者的 PFS 和 OS 与对照组相比。PFS 和 OS 的合并 HR (PARPi 与对照组) 分别为 0.63(95%CI,0.55-0.73)和 0.83(95%CI,0.73 至 -0.95)。在安全性方面,PARPi 表现出可控的不良反应。PARPi 组与对照组之间的总 AEs 或≥3 级 AEs 无显著差异。
我们的结果证实了 PARPi 在 BRCA 突变型乳腺癌患者中的疗效和安全性,更具体地阐明了 PARPi 单独或联合其他化疗药物的疗效。[图:见正文]。