具有 BRCA1/2 缺陷的癌细胞对聚 (ADP-核糖) 聚合酶 (PARP) 抑制剂敏感。我们评估了他拉佐帕尼对 DNA 损伤修复 (DDR) 改变患者的疗效。在这项 II 期试验中，患者根据分子改变被纳入四个队列之一：(1) 体细胞 BRCA1/2、(2) 其他同源重组修复途径、(3) PTEN 和 (4) 种系 BRCA1/2。主要终点是临床获益率 (CBR)：完全缓解、部分缓解或疾病稳定≥24 周。共有 79 名接受中位数治疗 4 种疗法的患者入组。队列 1-4 的 CBR 分别为：32.5%、19.7%、9.4% 和 30.6%。 PTEN 突变与生存率降低和进展时间缩短的趋势相关。Talazoparib 在选定的 DDR 改变的患者中显示出临床益处。 PTEN 突变/缺失患者获得的临床获益有限。需要进一步研究来确定 PTEN 是否可以预测或预测 PARP 抑制剂的反应。© 2024。作者。

Cancer cells with BRCA1/2 deficiencies are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We evaluated the efficacy of talazoparib in DNA-Damage Repair (DDR)-altered patients. In this phase II trial, patients were enrolled onto one of four cohorts based on molecular alterations: (1) somatic BRCA1/2, (2) other homologous recombination repair pathway, (3) PTEN and (4) germline BRCA1/2. The primary endpoint was a clinical benefit rate (CBR): complete response, partial response or stable disease ≥24 weeks. 79 patients with a median of 4 lines of therapy were enrolled. CBR for cohorts 1-4 were: 32.5%, 19.7%, 9.4% and 30.6%, respectively. PTEN mutations correlated with reduced survival and a trend towards shorter time to progression.Talazoparib demonstrated clinical benefit in selected DDR-altered patients. PTEN mutations/loss patients derived limited clinical benefit. Further study is needed to determine whether PTEN is prognostic or predictive of response to PARP inhibitors.© 2024. The Author(s).