Piha-Paul Sarina A, Tseng Chieh, Leung Cheuk Hong, Yuan Ying, Karp Daniel D, Subbiah Vivek, Hong David, Fu Siqing, Naing Aung, Rodon Jordi, Javle Milind, Ajani Jaffer A, Raghav Kanwal P, Somaiah Neeta, Mills Gordon B, Tsimberidou Apostolia M, Zheng Xiaofeng, Chen Ken, Meric-Bernstam Funda
Department of Investigational Cancer Therapeutics (A Phase I Clinical Trials Program), University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
NPJ Precis Oncol. 2024 Jul 31;8(1):166. doi: 10.1038/s41698-024-00634-6.
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.
具有BRCA1/2缺陷的癌细胞对聚（ADP-核糖）聚合酶（PARP）抑制剂敏感。我们评估了他拉唑帕尼在DNA损伤修复（DDR）改变的患者中的疗效。在这项II期试验中，根据分子改变将患者纳入四个队列之一：（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。79例患者入组，中位接受过4线治疗。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疾病进展时间缩短的趋势相关。他拉唑帕尼在选定的DDR改变的患者中显示出临床获益。PTEN突变/缺失的患者获得的临床获益有限。需要进一步研究以确定PTEN是PARP抑制剂反应的预后指标还是预测指标。
