Abstract 107P
Background
Approximately 10% of pancreatic ductal adenocarcinoma (PDAC) cases lacks KRAS mutations (KRASWT). Among these, only a small subgroup presents druggable genomic alterations, raising the question of when to apply large next-generation DNA sequencing (NGS) panels. Early-onset PDAC (≤45 years) is increasing globally, with recent findings showing an enrichment of KRASWT status in these patients.
Methods
This retrospective observational study utilized secondary data entered into a predefined database. FoundationOne CDx or Liquid gene panel sequencing was used to identify genomic alterations in patients who had failed standard treatments. Cases were classified by KRAS status, and KRASWT patients were stratified into early-onset (≤45 years) and late-onset (>45 years) groups. Alterations were evaluated using the ESMO Scale of Clinical Actionability for molecular Targets (ESCAT).
Results
NGS was performed on 181 PDAC and 8 pancreatic acinar cell carcinoma patients (ACC). Among PDAC patients, 21.5% (39/181) were KRASWT. Co-mutations in TP53, CDKN2A/B, and SMAD4 were more frequent in KRAS-mutant PDACs compared to KRASWT (p < 0.05). KRASWT patients showed a trend towards improved median overall survival (26 vs 18 months). Actionable TIER I-III alterations were more common in KRASWT patients (28.21% vs 14.08%), with fusion genes exclusively found in KRASWT (7.7% vs 0%). Early-onset KRASWT PDACs had a significantly higher incidence of gene fusions compared to late-onset ones (40% vs 2.9%).
Conclusions
Early-onset KRASWT PDACs frequently harbor actionable mutations, underscoring the importance of comprehensive genomic profiling to enable targeted therapeutic interventions in this patients’ population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
D. Melisi: Financial Interests, Personal, Advisory Board: Incyte co., Servier, iOnctura, Taiho; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Research Grant: iOnctura. All other authors have declared no conflicts of interest.