Taghizadeh Hossein, Müllauer Leonhard, Mader Robert M, Schindl Martin, Prager Gerald W
Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Austria.
Comprehensive Cancer Center Vienna, Austria.
Ther Adv Med Oncol. 2020 Jul 10;12:1758835920938611. doi: 10.1177/1758835920938611. eCollection 2020.
Metastatic pancreatic ductal adenocarcinoma (mPDAC) bears a dismal prognosis due to the limited activity of systemic chemotherapy. In our platform for precision medicine, we aim to offer molecular-guided treatments to patients without further standard therapy options.
In this single center, real-world retrospective analysis of our platform, we describe the molecular-based therapy approaches used in all 50 patients diagnosed with therapy-refractory mPDAC. A molecular portrait of the tumor specimens was created by next-generation sequencing, immunohistochemistry (IHC), microsatellite instability (MSI) testing, and fluorescence hybridization.
In total, we detected 123 mutations in 50 patients. The five most frequent mutations were ( = 40; 80%), ( = 29; 58%), ( = 8; 16%), ( = 4; 8%), and ( = 4; 8%), which together accounted for 40.2% of all mutations. Two patients had gene fusions, namely, and . IHC detected expression of EGFR, phosphorylated mTOR, and PTEN in 36 (72%), 33 (66%), and 17 patients (34%), respectively. For 14 (28%) of the 50 patients, a targeted therapy was suggested based on the identified molecular targets. The recommended treatments included the mTOR inhibitor everolimus ( = 3), pembrolizumab ( = 3), palbociclib ( = 2), nintedanib ( = 2), and cetuximab, crizotinib, tamoxifen, and the combination of lapatinib and trastuzumab, in one patient each.Finally, five patients received the recommended therapy. Four patients died due to disease progression before radiological assessment. One patient was treated with nintedanib and achieved stable disease for 6 months.
Based on our observations, precision medicine approaches are feasible and implementable in clinical routine and may provide molecular-based therapy recommendations for mPDAC.
由于全身化疗活性有限，转移性胰腺导管腺癌（mPDAC）的预后很差。在我们的精准医疗平台中，我们旨在为没有进一步标准治疗选择的患者提供分子导向治疗。
在对我们平台进行的这项单中心、真实世界回顾性分析中，我们描述了所有50例被诊断为难治性mPDAC患者所采用的基于分子的治疗方法。通过下一代测序、免疫组织化学（IHC）、微卫星不稳定性（MSI）检测和荧光杂交创建肿瘤标本的分子图谱。
我们总共在50例患者中检测到123个突变。最常见的五个突变是KRAS（n = 40；80%）、NRAS（n = 29；58%）、BRAF（n = 8；16%）、PIK3CA（n = 4；8%）和CTNNB1（n = 4；8%），它们总共占所有突变的40.2%。两名患者存在基因融合，即RET和NTRK1。免疫组织化学分别在36例（72%）、33例（66%）和17例患者（34%）中检测到EGFR、磷酸化mTOR和PTEN的表达。对于50例患者中的14例（28%），基于所确定的分子靶点建议进行靶向治疗。推荐的治疗包括mTOR抑制剂依维莫司（n = 3）、帕博利珠单抗（n = 3）、哌柏西利（n = 2）、尼达尼布（n = 2），以及西妥昔单抗、克唑替尼、他莫昔芬，还有1例患者接受拉帕替尼和曲妥珠单抗联合治疗。最后，5例患者接受了推荐治疗。4例患者在影像学评估前因疾病进展死亡。1例患者接受尼达尼布治疗，疾病稳定6个月。
基于我们的观察，精准医疗方法在临床常规中是可行且可实施的，并且可能为mPDAC提供基于分子的治疗建议。
