Guo Andong, Wu Chenrui, Cao Jishuang, Zhu Kejia, Ding Sentai
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Front Genet. 2024 Dec 6;15:1505163. doi: 10.3389/fgene.2024.1505163. eCollection 2024.
This study evaluated the real-world efficacy and safety of combining PARP inhibitors with novel hormonal therapy (NHT) as a first-line treatment in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene mutations.
We enrolled 41 mCRPC patients who received at least 1 month of combined treatment with PARP inhibitors and NHT. Patients were divided into two groups: Cohort A (mutations in BRCA1, BRCA2, or ATM genes) and Cohort B (mutations in other HRR genes). The primary endpoint was imaging-based progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS), PSA50 response, and adverse events (AEs). To ensure accurate research results and control confounding factors, we will employ multivariate Cox proportional hazards models to evaluate key variables affecting mCRPC patient survival outcomes.
This study enrolled 41 patients, 22 in Cohort A and 19 in Cohort B. The median PFS for all patients was 21.8 months, and the median OS had yet to be reached. The overall ORR was 48.8%, and the DCR was 61.0%. Specifically, the median PFS for Cohort A was 21.8 months compared to 14.5 months for Cohort B. The median OS had yet to be reached for either cohort. Regarding efficacy, 81.8% of patients in Cohort A and 73.7% in Cohort B achieved a PSA50 response. Imaging assessments showed ORRs of 54.6% for Cohort A and 42.1% for Cohort B, with DCRs of 72.7% and 47.4%, respectively. 85.4% of patients experienced grade 1 or 2 adverse events, and 51.2% encountered grade 3 or 4. In the multivariate Cox regression analysis focusing on PFS, the Gleason score was identified as a significant predictor (HR = 5.8, 95% CI: 1.65-20.2, = 0.006).
Combined first-line treatment with PARP inhibitors and NHT is effective and well-tolerated in mCRPC patients with HRR gene mutations, particularly those with BRCA1, BRCA2, or ATM mutations. These findings underscore the potential of this therapeutic combination in managing mCRPC in the Chinese population, suggesting a favorable outcome for those with specific genetic backgrounds.
本研究评估了聚（ADP-核糖）聚合酶（PARP）抑制剂与新型激素疗法（NHT）联合作为一线治疗方案，用于治疗携带同源重组修复（HRR）基因突变的中国转移性去势抵抗性前列腺癌（mCRPC）患者的真实世界疗效和安全性。
我们纳入了41例接受PARP抑制剂和NHT联合治疗至少1个月的mCRPC患者。患者分为两组：A组（BRCA1、BRCA2或ATM基因突变）和B组（其他HRR基因突变）。主要终点是基于影像学的无进展生存期（PFS），次要终点包括客观缓解率（ORR）、疾病控制率（DCR）、总生存期（OS）、PSA50缓解以及不良事件（AE）。为确保准确的研究结果并控制混杂因素，我们将采用多变量Cox比例风险模型来评估影响mCRPC患者生存结局的关键变量。
本研究共纳入41例患者，A组22例，B组19例。所有患者的中位PFS为21.8个月，中位OS尚未达到。总体ORR为48.8%，DCR为61.0%。具体而言，A组的中位PFS为21.8个月，B组为14.5个月。两组的中位OS均尚未达到。在疗效方面，A组81.8%的患者和B组73.7%的患者实现了PSA50缓解。影像学评估显示，A组的ORR为54.6%，B组为42.1%，DCR分别为72.7%和47.4%。85.4%的患者经历了1级或2级不良事件，51.2%的患者遭遇了3级或4级不良事件。在针对PFS的多变量Cox回归分析中， Gleason评分被确定为一个显著的预测因素（HR = 5.8，95% CI：1.65 - 20.2，P = 0.006）。
PARP抑制剂与NHT联合一线治疗对于携带HRR基因突变的mCRPC患者，尤其是携带BRCA1、BRCA2或ATM基因突变的患者，是有效且耐受性良好的。这些发现强调了这种治疗组合在中国人群中治疗mCRPC的潜力，表明具有特定遗传背景的患者可能会有良好的预后。
