Department of Medicine, Icahn School of Medicine at Mount Sinai (Morningside/West), New York, New York, USA,
Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Oncol Res Treat. 2023;46(5):211-215. doi: 10.1159/000529919. Epub 2023 Mar 7.
Despite major advances in surveillance and management, advanced cholangiocarcinoma (CCA) still carries a dismal prognosis. In recent years, several actionable genomic alterations in pancreatobiliary malignancies have been identified. For instance, homologous recombination deficiency (HRD) has been considered a predictive biomarker of clinical response to platinum and poly (ADP-ribose) polymerase (PARP) inhibitors.
A 53-year-old man with a stage 3 (T4N0M0) BRCA2-mutant CCA developed intolerable toxicity after 44 cycles of gemcitabine/cisplatin. In light of his HRD positivity, treatment was switched to single-agent olaparib. The patient showed a partial radiological response, which was maintained after 8 months of olaparib discontinuation (progression-free survival >36 months).
Given the durable response observed, olaparib can be a valuable therapeutic tool in BRCA-mutant CCAs. Ongoing and future clinical trials are needed to confirm the role of PARP inhibition in similar patients and to define the clinicopathological and molecular profile of the individuals most likely to benefit.
尽管在监测和管理方面取得了重大进展，但晚期胆管癌（CCA）的预后仍然很差。近年来，已鉴定出几种可治疗的胰腺胆道恶性肿瘤的基因组改变。例如，同源重组缺陷（HRD）已被认为是铂类和聚（ADP-核糖）聚合酶（PARP）抑制剂临床反应的预测生物标志物。
一名 53 岁男性，患有 3 期（T4N0M0）BRCA2 突变型 CCA，在接受 44 个周期的吉西他滨/顺铂治疗后出现无法耐受的毒性。鉴于他的 HRD 阳性，治疗改为单药奥拉帕利。患者表现出部分放射学反应，在停用奥拉帕利 8 个月后仍保持缓解（无进展生存期>36 个月）。
鉴于观察到的持久反应，奥拉帕利可能是 BRCA 突变型 CCA 的一种有价值的治疗工具。需要进行正在进行和未来的临床试验，以确认 PARP 抑制在类似患者中的作用，并确定最有可能受益的个体的临床病理和分子特征。
