Lena Jeanne, Alamé Mélissa, Italiano Antoine, Soubeyran Isabelle, Blouin Laura, Khalifa Emmanuel, Cousin Sophie, Pernot Simon, Palmieri Lola-Jade
Department of Medicine, Institut Bergonié, Bordeaux, France.
Department of Pathology, Institut Bergonié, Bordeaux, France.
Eur J Cancer. 2025 Feb 5;216:115197. doi: 10.1016/j.ejca.2024.115197. Epub 2024 Dec 21.
Molecular profiling is increasingly implemented to guide treatment of advanced pancreatic ductal adenocarcinoma (PDAC), especially when for clinical trials enrollment. This study aimed to describe actionable alterations detected in KRAS mutated (KRASm) versus KRAS wild-type (KRASwt) PDAC, the latter group being considered enriched in molecular alterations.
This prospective monocentric study included patients with locally advanced or metastatic PDAC who underwent next-generation sequencing (NGS) on liquid biopsy and/or tissue samples between 2015 and 2023, as part of the BIP academic study (NCT02534649). Actionable alterations were classified using the ESCAT (ESMO Scale for Clinical Actionability of molecular Targets).
A total of 378 patients with a PDAC underwent NGS: 73 on tissue samples, 162 on liquid biopsies, and 143 on both tissue and liquid. Liquid biopsies had a 59.3 % performance (181 informative samples out of 305). Among 318 informative NGS samples, 273 (86 %) were KRASm, and 45 (14 %) were KRASwt. Median overall survival (OS) was 19.35 in KRASwt patients and 16.89 months for KRASm patients (HR 0.67, 95 %CI (0.49-0.90), p = 0.02). ESCAT alterations were found in 15.7 % of total population, with 31.1 % in KRASwt tumors and 13.2 % in KRASm tumors. BRCA1/2 mutations were identified in 7.5 % of the population, and one NTRK fusion was found in a KRASwt PDAC. The molecular tumor board considered 71 patients (22.3 %) eligible for early-phase trials, with 14 treated with matched therapy.
Although actionable mutations were more frequent in KRASwt tumors, 13.2 % of KRASm PDAC harbored ESCAT alterations, emphasizing the importance of molecular profiling regardless of KRAS status.
分子谱分析越来越多地用于指导晚期胰腺导管腺癌（PDAC）的治疗，尤其是在临床试验入组时。本研究旨在描述在KRAS突变型（KRASm）与KRAS野生型（KRASwt）PDAC中检测到的可操作改变，后一组被认为分子改变更为丰富。
这项前瞻性单中心研究纳入了2015年至2023年间接受局部晚期或转移性PDAC的患者，他们作为BIP学术研究（NCT02534649）的一部分，接受了液体活检和/或组织样本的二代测序（NGS）。使用ESCAT（分子靶点临床可操作性的ESMO量表）对可操作改变进行分类。
共有378例PDAC患者接受了NGS检测：73例进行了组织样本检测，162例进行了液体活检，143例同时进行了组织和液体检测。液体活检的性能为59.3%（305个样本中有181个信息丰富的样本）。在318个信息丰富的NGS样本中，273例（86%）为KRASm，45例（14%）为KRASwt。KRASwt患者的中位总生存期（OS）为19.35个月，KRASm患者为16.89个月（HR 0.67，95%CI（0.49 - 0.90），p = 0.02）。在总人群的15.7%中发现了ESCAT改变，KRASwt肿瘤中为31.1%，KRASm肿瘤中为13.2%。在7.5%的人群中鉴定出BRCA1/2突变，在一例KRASwt PDAC中发现了一个NTRK融合。分子肿瘤委员会认为71例患者（22.3%）符合早期试验条件，其中14例接受了匹配治疗。
尽管可操作突变在KRASwt肿瘤中更常见，但13.2%的KRASm PDAC存在ESCAT改变，强调了无论KRAS状态如何，分子谱分析的重要性。
