Tarabay Anthony, Boileve Alice, Smolenschi Cristina, Antoun Leony, Valery Marine, Fuerea Alina, Perret Audrey, Burtin Pascal, Cosconea Simona, Belkhodja Hichem, Malka David, Boige Valérie, Hollebecque Antoine, Ducreux Michel
Gustave Roussy, Département de Médecine, 94805 Villejuif, France.
Gustave Roussy, Département d'Innovation Thérapeutique et d'Essais Précoces, 94805 Villejuif, France.
Biomedicines. 2023 Sep 19;11(9):2569. doi: 10.3390/biomedicines11092569.
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC, some of which are considered for molecular targeted therapies (MTTs), with potential clinical benefits and improved outcomes. However, the applicability of molecular profiling (MP) for precision medicine in PDAC remains to be demonstrated.
We conducted a retrospective analysis of all patients, aged ≥18 years with histologically confirmed PDAC, who underwent tumor MP between 2010 and 2020 in our institution as part of personalized medicine trials. The primary study endpoint was overall survival (OS), and (minimal follow-up was 6 months after MP).
Of 115 eligible patients, MP was successful in 102 patients (89%). KRAS mutations were the most frequent GAs, mostly G12D. Based on ESCAT classification, actionable GAs were found in 29 patients (28%), involving mainly or (5 (18%)), (5 (18%)), (5 (18%)), and (3 (11%)). Only 12 of these 29 patients (41%, or 10% of the whole population) received MTTs, with a median progression-free survival of 1.6 months. Median OS was 19 months in patients with actionable GAs treated with MTTs ( = 12 (11.8%)), 14 months in patients with actionable GAs treated with standard therapies ( = 17 (16.7%)), and 17 months in patients without actionable GAs treated with standard therapies ( = 73 (71.5%); = 0.26). The absence of liver metastases was associated with better OS (HR = 0.471, = 0.01). The highest OS following MTT was observed in patients with BRCA mutations treated with olaparib.
Actionable GAs were found in more than a quarter of patients with advanced PDAC. Overall, targeting actionable GAs with MTTs was not associated with improved OS in this retrospective study with limited patient numbers. However, selected GA/MTT combinations (e.g., BRCA mutations/olaparib) were associated with a better outcome.
胰腺导管腺癌（PDAC）是全球癌症死亡的第三大主要原因。大多数患者在诊断时已处于局部晚期或转移性疾病阶段，缺乏治疗选择。基因改变（GAs）在PDAC中经常被观察到，其中一些被考虑用于分子靶向治疗（MTTs），可能具有临床益处并改善预后。然而，分子谱分析（MP）在PDAC精准医学中的适用性仍有待证明。
我们对所有年龄≥18岁、组织学确诊为PDAC且在2010年至2020年期间在我们机构接受肿瘤MP检测的患者进行了回顾性分析，该检测作为个性化医学试验的一部分。主要研究终点是总生存期（OS），（MP检测后最短随访时间为6个月）。
115例符合条件的患者中，102例（89%）成功进行了MP检测。KRAS突变是最常见的基因改变，主要是G12D。根据ESCAT分类，在第29例患者（28%）中发现了可操作的基因改变，主要涉及 或 （5例（18%））、 （5例（18%））、 （5例（18%））和 （3例（11%））。这29例患者中只有12例（41%，占总人群的10%）接受了MTTs治疗，无进展生存期的中位数为1.6个月。接受MTTs治疗的有可操作基因改变的患者的OS中位数为19个月（ = 12例（11.8%）），接受标准治疗的有可操作基因改变的患者的OS中位数为14个月（ = 17例（16.7%）），接受标准治疗的无可操作基因改变的患者的OS中位数为17个月（ = 73例（71.5%）； = 0.26）。无肝转移与更好的OS相关（HR = 0.471， = 0.01）。在接受奥拉帕尼治疗的BRCA突变患者中观察到MTTs治疗后最高的OS。
在超过四分之一的晚期PDAC患者中发现了可操作的基因改变。总体而言，在这项患者数量有限的回顾性研究中，用MTTs靶向可操作的基因改变与OS改善无关。然而，选定GA/MTT组合（例如，BRCA突变/奥拉帕尼）与更好的预后相关。
