PDF(Pubmed)
Abstract：
UNASSIGNED: Cholangiocarcinoma (CCA) is an increasingly prevalent malignancy worldwide, with poor outcomes even when diagnosed at an early stage. While recent trials have shown benefit from the addition of immunotherapy to standard-of-care chemotherapy, the improvement in overall survival is modest. Multiple novel therapies for advanced CCA targeting actionable genetic alterations have been approved in recent years; BRCA1/2 mutations are identified in up to 5% of CCA patients and may be an additional target for novel treatment approaches. While BRCA mutations have been shown in clinical trials to predict response to poly(ADP-ribose) polymerase (PARP) inhibitors in several solid tumors including breast, ovarian, prostate, and pancreas, no similar large-scale trials have been published in CCA to date. We report here a durable response to PARP inhibitor monotherapy in BRCA-mutated extrahepatic CCA; to our knowledge, this is the second report of first-line PARP inhibitor monotherapy and the first reported use of the second-generation PARP inhibitor talazoparib in this setting.
UNASSIGNED: We report the case of a 79-year-old man with metastatic extrahepatic CCA harboring a somatic BRCA1 mutation who declined chemotherapy and was instead treated in the first-line metastatic setting with the PARP inhibitor talazoparib; he experienced a complete radiographic response six months into treatment and has remained on talazoparib for over three years without evidence of disease recurrence.
UNASSIGNED: This case adds to a growing list of retrospective studies supporting the clinical activity of PARP inhibitors in BRCA-mutated extrahepatic CCA. However, prospective data are clearly needed prior to adoption of this strategy in clinical practice. Fortunately, multiple trials investigating novel combination therapies utilizing PARP inhibitors in CCA are underway.
UNASSIGNED: We report the case of a 79-year-old man with metastatic extrahepatic CCA harboring a somatic BRCA1 mutation who declined chemotherapy and was instead treated in the first-line metastatic setting with the PARP inhibitor talazoparib; he experienced a complete radiographic response six months into treatment and has remained on talazoparib for over three years without evidence of disease recurrence.
UNASSIGNED: This case adds to a growing list of retrospective studies supporting the clinical activity of PARP inhibitors in BRCA-mutated extrahepatic CCA. However, prospective data are clearly needed prior to adoption of this strategy in clinical practice. Fortunately, multiple trials investigating novel combination therapies utilizing PARP inhibitors in CCA are underway.
摘要：
■胆管癌（CCA）是全球范围内越来越普遍的恶性肿瘤，即使在早期诊断，结果也很差。虽然最近的试验表明，在标准治疗化疗中加入免疫治疗是有益的，总体生存率改善不大.近年来，针对晚期CCA靶向可操作的遗传改变的多种新疗法已获得批准；在多达5％的CCA患者中鉴定出BRCA1/2突变，并且可能是新治疗方法的另一个靶标。虽然BRCA突变已在临床试验中显示可预测在包括乳腺在内的几种实体瘤中对聚（ADP-核糖）聚合酶（PARP）抑制剂的反应，卵巢,前列腺,还有胰腺,迄今为止,CCA还没有发表类似的大规模试验.我们在这里报告了在BRCA突变的肝外CCA中对PARP抑制剂单一疗法的持久反应；据我们所知，这是第二份关于一线PARP抑制剂单药治疗的报告,也是首次报道在这种情况下使用第二代PARP抑制剂他唑帕尼.
■我们报告了一例79岁的患有转移性肝外CCA的男性患者，该患者具有体细胞BRCA1突变，他拒绝了化疗，而是在一线转移环境中使用PARP抑制剂talazoparib进行了治疗；他在治疗六个月后经历了完全的放射学反应，并且已经使用talazoparib治疗了三年以上，没有疾病复发的证据。
■该病例增加了越来越多的回顾性研究，支持PARP抑制剂在BRCA突变的肝外CCA中的临床活性。然而,在临床实践中采用该策略之前,显然需要前瞻性数据.幸运的是,正在进行多项研究CCA中使用PARP抑制剂的新型联合疗法的试验.
■我们报告了一例79岁的患有转移性肝外CCA的男性患者，该患者具有体细胞BRCA1突变，他拒绝了化疗，而是在一线转移环境中使用PARP抑制剂talazoparib进行了治疗；他在治疗六个月后经历了完全的放射学反应，并且已经使用talazoparib治疗了三年以上，没有疾病复发的证据。
■该病例增加了越来越多的回顾性研究，支持PARP抑制剂在BRCA突变的肝外CCA中的临床活性。然而,在临床实践中采用该策略之前,显然需要前瞻性数据.幸运的是,正在进行多项研究CCA中使用PARP抑制剂的新型联合疗法的试验.
