Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Petah Tiqwa, Israel,
Foundation Medicine Inc., Cambridge, Massachusetts, USA.
Oncol Res Treat. 2021;44(1-2):20-27. doi: 10.1159/000511919. Epub 2020 Dec 4.
BACKGROUND/AIMS: Current chemotherapy regimens for cholangiocarcinoma (CCA) yield poor outcomes, with a median overall survival of <12 months. Recent data on the genomic landscape of CCAs have created opportunities for targeted therapy. Yet, data regarding its efficacy are scarce. We aimed to describe the genomic landscape of a CCA patient cohort using next-generation sequencing (NGS), focusing on the ERBB/EFGR pathway and assessing response to anti-HER2 agents.
Tissue samples of intrahepatic CCA (IHCC) and extrahepatic CCA (EHCC) underwent NGS for somatic aberrations. The clinical outcomes for patients treated with anti-HER2 agents were evaluated.
A total of 1,863 CCA cases (1,615 IHCCs and 248 EHCCs) underwent NGS, and they revealed a high prevalence of ERBB alterations (IHCC, 4.2%; EHCC, 9.7%). Among these, 23.8% of the IHCCs and 53.6% of the EHCCs had a point mutation in ERBB2, and 66.6% of the IHCCs and 41.2% of the EHCCs had ERBB copy number amplification. Three EHCC patients were diagnosed at our institute with ERBB/EGFR aberrations; 2 patients were treated with neratinib and 1 patient with a chemotherapy-trastuzumab combination. All 3 achieved disease stabilization and a clinical benefit. One patient underwent a liquid biopsy before and after 3 months of treatment, demonstrating disappearance of the ERBB2 clone and emergence of a Myc-mutated clone after treatment.
The genomic landscape of CCAs may harbor targetable alterations, especially in the ERBB/EGFR pathway. These alterations may have clinical significance in everyday practice.
背景/目的：目前用于胆管癌（CCA）的化疗方案疗效不佳，中位总生存期<12 个月。最近关于 CCA 基因组图谱的数据为靶向治疗创造了机会。然而，关于其疗效的数据仍然很少。我们旨在使用下一代测序（NGS）描述 CCA 患者队列的基因组图谱，重点关注 ERBB/EFGR 通路，并评估抗 HER2 药物的反应。
对肝内 CCA（IHCC）和肝外 CCA（EHCC）的组织样本进行 NGS 以检测体细胞异常。评估接受抗 HER2 药物治疗的患者的临床结局。
共有 1863 例 CCA 病例（1615 例 IHCC 和 248 例 EHCC）进行了 NGS，结果显示 ERBB 改变的发生率很高（IHCC，4.2%；EHCC，9.7%）。其中，IHCC 的 ERBB2 点突变率为 23.8%，EHCC 的 ERBB2 点突变率为 53.6%；IHCC 的 ERBB 拷贝数扩增率为 66.6%，EHCC 的 ERBB 拷贝数扩增率为 41.2%。我们医院诊断了 3 例 EHCC 患者存在 ERBB/EGFR 异常，其中 2 例接受了 neratinib 治疗，1 例接受了化疗-曲妥珠单抗联合治疗。所有 3 例患者均达到疾病稳定并获得临床获益。1 例患者在治疗前和治疗 3 个月后进行了液体活检，显示 ERBB2 克隆消失，治疗后出现 Myc 突变克隆。
CCA 的基因组图谱可能存在可靶向的改变，特别是在 ERBB/EGFR 通路。这些改变在日常实践中可能具有临床意义。
