Clinical and molecular features of early-onset metastatic pancreatic cancer and their impact on therapeutic sequences: A multicenter study.

e16407 Background: Recently, there has been an increase in the incidence of early-onset PDAC (EO-PDAC), which is conventionally defined as cancer occurring in adults younger than 50 years. However, clinical and molecular data remain limited and inconsistent. Our study aimed to examine the differences in outcomes and molecular characteristics between EO-PDAC and late-onset pancreatic ductal adenocarcinoma (LO-PDAC) patients. Methods: We conducted a retrospective study involving 486 patients with metastatic pancreatic ductal adenocarcinoma across six different institutions in Italy. The study's primary objective was to evaluate the median overall survival of EO-PDAC patients compared to those with late-onset PDAC. Additionally, we aimed to assess median progression-free survival (mPFS), molecular profiles, and treatment sequences in both subgroups. Results: Of the patients, 80 (16.5%) were early onset and 406 (83.5%) were late onset. The median ages were 46 (±5) and 67 (±8) years, respectively. In the overall population, the median mOS was significantly lower in EO-PDAC patients: 10.0 versus 14.0 months ( p = 0.0103 ). Furthermore, the mPFS was also significantly lower in EO-PDAC patients: 4.0 versus 6.0 months ( p = 0.0132 ). Patients with EO-PDAC exhibited a higher prevalence of KRAS G12D and KRAS G12V mutations, at 31% and 24% respectively, compared to those with LO-PDAC. Finally, a higher percentage of LO-CRC patients continued to a second line (50.7% versus 48.6%). A percentage of 4.18% of LO-CRC patients started a fourth line, compared to 1.25% of EO-CRC. Conclusions: The results of our work showed a worse prognosis for EO-PDAC patients compared to LO-PDAC patients. This is associated with a different molecular profile and a lower percentage of patients reaching subsequent lines. Further research is necessary to better understand this expanding group of patients from molecular and therapeutic perspectives.