Mehdi Maahum, Szabo Aniko, Shreenivas Aditya, Thomas James P, Tsai Susan, Christians Kathleen K, Evans Douglas B, Clarke Callisia N, Hall William A, Erickson Beth, Ahmed Gulrayz, Thapa Bicky, McFall Thomas, George Ben, Kurzrock Razelle, Kamgar Mandana
Department of Medicine, Medical College of Wisconsin and the LaBahn Pancreatic Cancer Program, Milwaukee, WI, USA.
Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin and the LaBahn Pancreatic Cancer Program, Milwaukee, WI, USA.
Ther Adv Med Oncol. 2024 May 19;16:17588359241253113. doi: 10.1177/17588359241253113. eCollection 2024.
wild-type (WT) pancreatic ductal adenocarcinoma (PDAC) represents a distinct entity with unique biology. The therapeutic impact of matched targeted therapy in these patients in a real-world setting, to date, is less established.
The aim of our study was to review our institutional database to identify the prevalence of actionable genomic alterations in patients with -WT tumors and to evaluate the therapeutic impact of matched targeted therapy in these patients.
We reviewed electronic medical records of patients with PDAC and advanced disease ( = 14) who underwent clinical-grade tissue ± liquid next-generation sequencing (315-648 genes for tissue) between years 2015 and 2021.
Demographic and disease characteristics were summarized using descriptive parameters. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.
Of 236 PDAC patients, 14 had advanced/metastatic disease with tumors. Median age at diagnosis was 66 years. There was a high frequency of potentially actionable genomic alterations, including three (21%) with alterations, two (14%) with fusions [ and ( = 1 each)]; and one with a druggable ( E746_A755delISERD) variant; two other patients had an and a alteration. Five patients were treated with matched targeted therapy, with three having durable benefit: (i) erlotinib for -altered tumor, followed by osimertinib/capmatinib when amplification emerged (first-line therapy); (ii) pralsetinib for fusion (fifth line); and (iii) dabrafenib/trametinib for N486_P490del (third line). Duration of time on chemotherapy-free matched targeted therapy for these patients was 17+, 11, and 18+ months, respectively.
Sustained therapeutic benefit can be achieved in a real-world setting in a subset of patients with advanced/metastatic PDAC treated with chemotherapy-free matched targeted agents. Prospective studies are warranted.
野生型（WT）胰腺导管腺癌（PDAC）是一种具有独特生物学特性的独特实体。迄今为止，在现实环境中，匹配的靶向治疗对这些患者的治疗效果尚不明确。
本研究的目的是回顾我们机构的数据库，以确定WT肿瘤患者中可操作的基因组改变的发生率，并评估匹配的靶向治疗对这些患者的治疗效果。
我们回顾了2015年至2021年间接受临床级组织±液体二代测序（组织检测315 - 648个基因）的PDAC和晚期疾病患者（n = 14）的电子病历。
使用描述性参数总结人口统计学和疾病特征。采用Kaplan-Meier方法估计无进展生存期（PFS）和总生存期（OS）。
在236例PDAC患者中，14例患有晚期/转移性疾病且为WT肿瘤。诊断时的中位年龄为66岁。存在高频率的潜在可操作基因组改变，包括3例（21%）有KRAS改变，2例（14%）有融合[RET和NTRK1（各1例）]；1例有可靶向治疗的EGFR（E746_A755delISERD）变异；另外2例患者分别有BRAF和NRAS改变。5例患者接受了匹配的靶向治疗，3例有持久获益：（i）厄洛替尼用于KRAS改变的肿瘤，当出现EGFR扩增时改用奥希替尼/卡马替尼（一线治疗）；（ii）普拉替尼用于RET融合（五线治疗）；（iii）达拉非尼/曲美替尼用于BRAF N486_P490del（三线治疗）。这些患者接受无化疗的匹配靶向治疗的持续时间分别为17 +、11和18 +个月。
在现实环境中，一部分接受无化疗匹配靶向药物治疗的晚期/转移性WT PDAC患者可实现持续的治疗获益。有必要进行前瞻性研究。
