KRAS status in pancreatic ductal adenocarcinoma

In this video, Dr Justine Castaigne discusses a retrospective analysis of KRAS status in pancreatic ductal adenocarcinoma (PDAC), presented at ESMO GI 2026.¹ The study included 106 patients diagnosed with PDAC at Cliniques Universitaires Saint-Luc between July 2019 and March 2024, whose KRAS status was determined by next-generation sequencing. The primary objectives were to assess overall survival and clinical and molecular characteristics according to KRAS status. Progression-free survival was a secondary endpoint. 

In this cohort, 14 patients, representing approximately 13%, had KRAS wild-type tumours, while 92 patients had KRAS-mutated disease. Metastatic disease was frequent in both groups. Compared with the KRAS-mutated group, patients with KRAS wild-type PDAC more often had potentially actionable alterations, including BRAF, BRCA and EGFR mutations. 

Clinical outcomes appeared more favourable in the KRAS wild-type group. Overall survival was significantly longer compared with the KRAS-mutated group, with a median of 31.6 versus 14.1 months in the poster analysis. Progression-free survival was also longer, with a median of 12.8 versus 6.0 months. These findings suggest that KRAS wild-type PDAC may represent a distinct subgroup with better prognosis and more opportunities for targeted treatment. 

Dr Castaigne emphasises that these data support the importance of molecular profiling in PDAC, both to refine prognosis and to identify potential therapeutic targets. At the same time, she notes that the therapeutic landscape is rapidly changing with the development of RAS-directed therapies, which may increase the clinical relevance of KRAS status and further support precision medicine approaches in pancreatic cancer.