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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.
The field changed in 2026 when RASolute 302 showed that daraxonrasib, an inhibitor of the active form of all RAS proteins, lengthened survival over chemotherapy after first-line treatment; it is now approved and is being tested first line with and without chemotherapy and in the adjuvant setting. G12D-selective inhibitors (zoldonrasib, MRTX1133 and others) are in phase 3 first line, G12C inhibitors are used off label or in trials for the small G12C group, and shared KRAS vaccines, personalised mRNA vaccines, claudin 18.2 and mesothelin-directed antibodies, antibody-drug conjugates and CAR-T cells are in trials. Immune checkpoint inhibitors alone do not work outside mismatch repair deficient disease, and the search for combinations that make this immunologically cold tumour respond continues.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
Most pancreatic cancers arise in the head next to the bile duct, which is why jaundice is the presenting sign; bile duct cancers are named by where along the tree they sit.
Same organ: Glucagonoma, VIPoma, Somatostatinoma, Pancreatic ductal adenocarcinoma, Biliary tract cancer (cholangiocarcinoma), Intrahepatic cholangiocarcinoma, Extrahepatic cholangiocarcinoma (perihilar and distal), Biliary tract cancer (all types), Neuroendocrine tumours, Pancreatic neuroendocrine tumours, Grade 3 well-differentiated neuroendocrine tumour, Extrapulmonary neuroendocrine carcinoma, Gallbladder cancer, Gallbladder adenocarcinoma, Papillary carcinoma of the gallbladder, Mucinous carcinoma of the gallbladder, Adenosquamous and squamous carcinoma of the gallbladder, Neuroendocrine carcinoma of the gallbladder, Incidental gallbladder cancer (found after cholecystectomy), Carcinoma in situ and dysplasia of the gallbladder, Cystic duct carcinoma, Ampullary cancer (ampulla of Vater), Resectable pancreatic ductal adenocarcinoma, Borderline resectable pancreatic ductal adenocarcinoma, Locally advanced unresectable pancreatic ductal adenocarcinoma, KRAS G12C-mutant pancreatic ductal adenocarcinoma, KRAS wild-type pancreatic ductal adenocarcinoma, BRCA or PALB2-mutant pancreatic ductal adenocarcinoma, Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma, Pancreatic acinar cell carcinoma, Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors, Pancreatoblastoma, Adenosquamous carcinoma of the pancreas, Colloid (mucinous non-cystic) carcinoma of the pancreas, Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, Invasive carcinoma arising in an intraductal papillary mucinous neoplasm (IPMN-associated carcinoma), Mucinous cystic neoplasm of the pancreas with associated invasive carcinoma (MCN-associated carcinoma), Solid pseudopapillary neoplasm of the pancreas
Nothing recorded yet.
Background: CA 19-9. Also on OnCo: Symptoms and red flags · Early detection roadmap.
Modified FOLFIRINOX or NALIRIFOX (NAPOLI 3); gemcitabine plus nab-paclitaxel as the alternative, chosen by fitness, biliary drainage and neuropathy.
Gemcitabine plus nab-paclitaxel at reduced dose or gemcitabine alone; best supportive care when chemotherapy would do harm.
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.
Daraxonrasib after first-line chemotherapy (RASolute 302); otherwise switch backbone, liposomal irinotecan with fluorouracil after gemcitabine or a gemcitabine-based regimen after FOLFIRINOX.
Biliary stenting, pancreatic enzyme replacement, dietetic support, early palliative care, anticoagulation for thrombosis and coeliac plexus block for pain.
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.
Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Answer a few questions from a report and read the guideline statement that applies, quoted word for word with its source. Educational aids to prepare for an appointment, not advice.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
A swollen painful calf, or sudden breathlessness with chest pain; venous thromboembolism including pulmonary embolism is a labelled warning.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
Capecitabine: take within 30 minutes after a meal. DPD deficiency (DPYD variants) causes severe toxicity: pre-treatment genotyping is recommended in Europe.
See all on the product pages:Dabrafenib + trametinibDaraxonrasibFluorouracil (5-FU)FOLFIRINOX / mFOLFIRINOXGemcitabineGemcitabine + nab-paclitaxelIrinotecan (and liposomal irinotecan)NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)OlaparibPembrolizumabZoldonrasib·Printable cards in the navigator
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Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
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