Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Hunan Province, Changsha, 410005, People's Republic of China.
Department of Urology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, Fujian, People's Republic of China.
Sci Rep. 2024 Aug 27;14(1):19895. doi: 10.1038/s41598-024-70398-3.
Although overall survival data are still premature, the PROpel study found radiological progression-free survival (PFS) benefits of abiraterone and olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC). However, for patients who have not been genetically tested or lack BRCA1/2 mutations (BRCAm), this combination therapy has been questioned as a first-line conventional treatment for mCRPC, mainly due to significant health economics and side effects. In our retrospective study, we found that treatment with low-dose abiraterone plus olaparib as a late-line treatment for mCRPC could lead to prostate-specific antigen (PSA) and symptom PFS in selective cases even without BRCAm. The median PSA-PFS was 8 months (IQR: 6.5-11.5), with a median follow-up duration of 39.0 months (IQR: 27.5-64.5). Gene tests were conducted in all patients, identifying non-BRCA mutations through ctDNA testing (24%), tumor tissue testing (12%), or both (64%). Adverse events occurred in 72% of patients, with 16% experiencing Grade ≥ 3 events. Common adverse events included anemia (64%), decreased appetite (48%), and fatigue (25%). Our findings support low-dose abiraterone plus olaparib as a potential option for mCRPC patients without BRCAm, offering manageable safety and efficacy profiles.
虽然总生存数据仍不成熟,但 PROpel 研究发现,在转移性去势抵抗性前列腺癌(mCRPC)患者中,阿比特龙联合奥拉帕利可带来影像学无进展生存期(PFS)的获益。然而,对于未经基因检测或缺乏 BRCA1/2 突变(BRCAm)的患者,这种联合治疗作为 mCRPC 的一线常规治疗受到质疑,主要是由于其具有显著的健康经济学和副作用。在我们的回顾性研究中,我们发现对于 mCRPC 患者,采用低剂量阿比特龙联合奥拉帕利进行后线治疗,即使在没有 BRCAm 的情况下,也可在部分患者中带来前列腺特异性抗原(PSA)和症状 PFS 的获益。PSA-PFS 的中位数为 8 个月(IQR:6.5-11.5),中位随访时间为 39.0 个月(IQR:27.5-64.5)。所有患者均进行了基因检测,通过 ctDNA 检测(24%)、肿瘤组织检测(12%)或两者均检测(64%)识别出非 BRCA 突变。72%的患者发生了不良事件,16%的患者发生了≥3 级事件。常见的不良事件包括贫血(64%)、食欲下降(48%)和疲劳(25%)。我们的研究结果支持低剂量阿比特龙联合奥拉帕利作为无 BRCAm 的 mCRPC 患者的潜在选择,具有可管理的安全性和疗效特征。