Treatment algorithm for metastatic PDAC. FOLFIRINOX and gemcitabine/nab-paclitaxel are the current standard of care in first-line settings. If patients are initiated with FOLFIRINOX with disease control, consider maintenance therapy with 5-FU/FOLFIRI after a minimum of 4 months of FOLFIRINOX. If patients are initiated with gemcitabine/nab-paclitaxel with disease control, consider maintenance therapy with gemcitabine after a minimum of 3 months of gemcitabine/nab-paclitaxel. Second-line chemotherapy changes the backbone: initial treatment with FOLFIRINOX is gemcitabine-based, while initial treatment with gemcitabine/nab-paclitaxel is 5-FU-based. Where possible, determine the three ESCAT level I alterations (germline BRCA1/2, MSI-high, NTRAK).