Precision medicine strategy in pancreatic ductal adenocarcinoma

作者：Anthony Tarabay, L Swales, C. Smolenschi, Elie Akoury, Marine Valéry, Alina Fuerea, T. Pudlarz, V. Boige, Etienne Rouleau, Maximiliano Gelli, Mohamed Amine Bani, Rémy Barbe, Antoine Hollebecque, Michel Ducreux, Alice Boilève · 发表于：ESMO Open · 年份：2025 · DOI：10.1016/j.esmoop.2025.105899 · 被引用次数：3 · 研究领域：Pancreatic and Hepatic Oncology Research、Pancreatitis Pathology and Treatment、Peptidase Inhibition and Analysis

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited therapeutic options. Integration of molecular profiling may enable personalized treatment approaches. We evaluated the clinical utility of molecularly matched treatment (MMT) in a real-life cohort of PDAC patients. PATIENTS AND METHODS: A retrospective chart review of clinical/molecular data was carried out, including all PDAC patients with a contributive molecular profile. Survival outcomes were compared across three groups: patients with actionable molecular alterations (MAs) who received MMT (MA/MMT), patients with actionable alterations without MMT (MA/No MMT), and patients without actionable alterations (No MA/No MMT). RESULTS: Among 342 patients (median age 61 years; 48% female; 95% Eastern Cooperative Oncology Group 0-1), molecular profiling was carried out using tissue (50%), liquid biopsy (45%), or both (5%). The most common gene alterations were KRAS (84%), TP53 (72%), and CDKN2A (26%). Actionable alterations were found in 69 patients (20%), with 31 (45%) receiving MMT. Targeted therapies included notably olaparib (BRCA2), trastuzumab (HER2), and KRAS G12C inhibitors. Median overall survival (OS) from metastatic diagnosis was significantly longer in the MA/MMT group (32.9 months) compared with MA/No MMT (12.9 months) and No MA/No MMT groups (17.6 months) (P = 0.0008). From initial diagnosis, OS was 34.9, 27.1, and 21.5 months, respectively (P = 0.005). Median progression-free ...