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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Metastatic pancreatic cancer has spread beyond the pancreas, usually to the liver, and is treated with chemotherapy rather than surgery. Three combination regimens lengthen life, a minority of patients qualify for targeted drugs chosen by tumour or inherited mutations, and in 2026 the pan-RAS inhibitor daraxonrasib became the first drug against the KRAS mutation that drives almost every case.
Metastatic pancreatic ductal adenocarcinoma is diagnosed by CT with biopsy of the primary or a metastasis, usually under endoscopic ultrasound or CT guidance. Nearly every tumour carries a KRAS mutation (G12D, G12V and G12R most often, G12C in a small minority) alongside TP53, CDKN2A and SMAD4 loss, and every patient should have germline testing and tumour sequencing at diagnosis, because roughly one in ten has an actionable finding: a germline BRCA or PALB2 variant, mismatch repair deficiency, or, in KRAS wild-type tumours, a gene fusion or BRAF alteration. Supportive care runs in parallel: biliary stenting, pancreatic enzyme replacement, nutrition, pain control and treatment of thrombosis.
Gemcitabine became the standard in 1997 by improving symptoms and survival modestly over fluorouracil. Two combinations then beat it: FOLFIRINOX in PRODIGE 4/ACCORD 11 (2011) for fit patients, and gemcitabine plus nab-paclitaxel in MPACT (2013) for a broader group. NAPOLI 3 (2023) showed that NALIRIFOX, which replaces irinotecan with its liposomal form, beats gemcitabine plus nab-paclitaxel, and it was approved in 2024. Choice between them turns on fitness, neuropathy, biliary drainage and patient preference. Olaparib maintenance after platinum chemotherapy is approved for germline BRCA carriers (POLO), pembrolizumab for mismatch repair deficient tumours, zenocutuzumab for NRG1 fusions, and NTRK, BRAF and other targeted drugs for the rare tumours that carry them. Second-line chemotherapy switches backbone: liposomal irinotecan with fluorouracil after gemcitabine (NAPOLI-1), gemcitabine-based treatment after FOLFIRINOX.
| Setting | Approach | Guideline |
|---|---|---|
| First line, fit patients | Modified FOLFIRINOX or NALIRIFOX (NAPOLI 3); gemcitabine plus nab-paclitaxel as the alternative, chosen by fitness, biliary drainage and neuropathy. | not mapped |
| First line, less fit patients | Gemcitabine plus nab-paclitaxel at reduced dose or gemcitabine alone; best supportive care when chemotherapy would do harm. | not mapped |
| Maintenance and biomarker-directed therapy | Olaparib after at least sixteen weeks of platinum without progression in germline BRCA carriers (POLO); pembrolizumab for mismatch repair deficient tumours; zenocutuzumab for NRG1 fusions; NTRK and BRAF inhibitors where present. | not mapped |
| Second line | Daraxonrasib after first-line chemotherapy (RASolute 302); otherwise switch backbone, liposomal irinotecan with fluorouracil after gemcitabine or a gemcitabine-based regimen after FOLFIRINOX. | not mapped |
| Supportive care throughout | Biliary stenting, pancreatic enzyme replacement, dietetic support, early palliative care, anticoagulation for thrombosis and coeliac plexus block for pain. | not mapped |
| Clinical trials | First-line daraxonrasib with or without chemotherapy; G12D inhibitors with chemotherapy; KRAS vaccines; claudin 18.2 and mesothelin-directed antibodies and CAR-T; platform trials such as Precision Promise. | not mapped |