Loading
KRAS wild-type pancreatic cancer is the one in ten pancreatic cancers without the KRAS mutation that drives the rest. Instead many carry a different switched-on gene, often a fusion involving NRG1, NTRK, ALK, ROS1, FGFR2 or RET, or a BRAF change, and several of these have approved pills or antibodies, so these tumours must be sequenced with a test that detects fusions.
The absence of a KRAS mutation in a pancreatic ductal adenocarcinoma is a signal to look harder. Some cases are misclassified ampullary, distal bile duct or duodenal cancers, some are mismatch repair deficient, and a substantial share carry an alternative driver: fusions of NRG1 (the commonest), NTRK1 to 3, ALK, ROS1, FGFR2, RET, MET or BRAF, BRAF V600E mutations and in-frame BRAF deletions, or less often ERBB2 amplification or GNAS mutation in a cancer arising from an intraductal papillary mucinous neoplasm. Because fusions are missed by DNA panels with limited intron coverage, RNA-based sequencing or a comprehensive panel with fusion detection is recommended for every KRAS wild-type tumour.
Several of these drivers have drugs. Zenocutuzumab, a bispecific antibody blocking HER2 and HER3 that prevents NRG1 from signalling, produced durable responses in the eNRGy trial and was approved in December 2024 for NRG1 fusion-positive pancreatic cancer, the first targeted drug approved for a pancreatic driver. Larotrectinib and entrectinib are approved for NTRK fusions in any tumour, dabrafenib plus trametinib for BRAF V600E in any tumour, and ALK, ROS1, RET and FGFR2 inhibitors are used on the strength of their activity in other cancers; BRAF in-frame deletions respond to MEK inhibitors in case series. Chemotherapy remains the first-line standard while sequencing is arranged, and NOTABLE, a Chinese phase 3, showed that adding the EGFR antibody nimotuzumab to gemcitabine lengthened survival in KRAS wild-type disease, leading to a Chinese approval.
KRAS wild-type tumours also differ in biology: they are less dependent on the MAPK pathway, less likely to carry CDKN2A or SMAD4 loss, and their prognosis with chemotherapy is somewhat better. Open problems are that fusion testing is still not universal, that each driver is too rare for pancreatic-specific trials, and that resistance to the targeted drugs follows the patterns seen in lung cancer.
Roughly one in ten pancreatic ductal adenocarcinomas has no KRAS mutation. The group is younger on average and is where most of the gene fusions and BRAF alterations that can be targeted with existing drugs are found.
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, Metastatic pancreatic ductal adenocarcinoma, KRAS G12C-mutant 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.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Comprehensive genomic profiling with fusion detection (RNA sequencing where DNA panels are negative) for every KRAS wild-type tumour; pathology review to exclude a periampullary primary.
Chemotherapy as for other pancreatic adenocarcinoma while sequencing is completed; a targeted drug first line only for NTRK or NRG1 fusions where the patient is unfit for chemotherapy.
Zenocutuzumab (eNRGy), approved December 2024 for pancreatic cancer with an NRG1 fusion after prior systemic therapy.
Larotrectinib or entrectinib, approved for NTRK fusion-positive solid tumours; repotrectinib after resistance.
Dabrafenib plus trametinib for BRAF V600E (tumour-agnostic approval); MEK inhibitors for BRAF in-frame deletions on case-series evidence.
ALK, ROS1, RET and FGFR2 inhibitors extrapolated from other cancers; mismatch repair deficient tumours receive pembrolizumab.
Chemotherapy; nimotuzumab plus gemcitabine approved in China after NOTABLE.
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Every KRAS wild-type pancreatic cancer should be tested for NRG1 fusions because a specific, approved antibody now exists; zenocutuzumab is the first targeted drug approved for a pancreatic cancer driver.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
Together with the German MASTER report, this paper is why guidelines recommend comprehensive profiling with fusion detection in KRAS wild-type pancreatic cancer.
It fixed the working numbers for a comprehensive panel in pancreatic cancer: a hit worth acting on in about one patient in six, most of it in repair genes and the KRAS wild-type minority.
NTRK fusions are under 0.5% of pancreatic cancers but carry a tumour-agnostic approval; this case is the published proof that the label applies here.
KRAS wild-type status should trigger fusion testing, ideally by RNA sequencing, because NRG1 fusions can be targeted by HER-family inhibitors and now by zenocutuzumab.
ALK is the reason young, KRAS wild-type patients should have fusion testing even though the overall rate is one in six hundred.
It is the reference multi-platform dataset and the reason a KRAS wild-type report is treated as a search for another driver rather than as an absence.
Query for this cancer: (TITLE:"KRAS wild-type pancreatic ductal adenocarcinoma" OR ABSTRACT:"KRAS wild-type pancreatic ductal adenocarcinoma" OR TITLE:"KRAS wild-type pancreatic cancer" OR ABSTRACT:"KRAS wild-type pancreatic cancer" OR TITLE:"KRAS-negative PDAC" OR ABSTRACT:"KRAS-negative PDAC" OR TITLE:"Fusion-driven pancreatic cancer" OR ABSTRACT:"Fusion-driven pancreatic cancer" OR TITLE:"BRAF-altered pancreatic cancer" OR ABSTRACT:"BRAF-altered pancreatic cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about KRAS wild-type pancreatic ductal adenocarcinoma, not a curated reading list.
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.
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.
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.
Avoid grapefruit.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
See all on the product pages:Dabrafenib + trametinibEntrectinibFOLFIRINOX / mFOLFIRINOXGemcitabineGemcitabine + nab-paclitaxelNALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)PembrolizumabRepotrectinib·Printable cards in the navigator
Newly diagnosed? Read the first 60 days with KRAS wild-type pancreatic ductal adenocarcinoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
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.
Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked.