Real-world clinical outcome of unresectable locally advanced & de-novo metastatic pancreatic ductal adenocarcinoma: a multicentre retrospective study

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited treatment options yielding poor outcomes. This study aimed to evaluate the real-world clinical characteristics, treatment patterns, and outcomes of patients with locally advanced unresectable and de-novo metastatic PDAC in Saudi Arabia, providing regional data to compare with international benchmarks. Methods: This is a retrospective, multicentre study involving 350 patients diagnosed with unresectable locally advanced or de-novo metastatic PDAC between January 2015 and November 2023. Data were collected from 10 oncology centers across Saudi Arabia. Results: The median age at diagnosis was 60 years, with 63% of patients presenting with multiple metastatic sites, primarily in the liver (66.3%). FOLFIRINOX was the most common first-line treatment (55.1%), followed by gemcitabine plus nab-paclitaxel (15.1%). The median PFS for first-line treatment was 5.3 months, with FOLFIRINOX achieving the longest PFS (6.5 months). The median OS was 10.34 months for the entire cohort, with better survival outcomes observed in patients receiving FOLFIRINOX (12.3 months). Independent prognostic factors for PFS and OS included performance status, first-line regimen, and neutrophil-lymphocyte ratio (NLR). Among patients tested, 7.1% had deficient mismatch repair (d-MMR), and 5.8% harbored BRCA mutations. Conclusions: This real-world study confirms that clinical outcomes for locally advanced unresectable and metastatic PDAC in Saudi Arabia are consistent with international data, with FOLFIRINOX showing superior outcomes over gemcitabine-based regimens. However, both treatments reflect the persistent poor prognosis of PDAC, underscoring the need for novel therapeutic strategies. Further research is warranted to optimize treatment selection and improve survival outcomes in this population.