Loading
KRAS G12C pancreatic cancer is the small slice of pancreatic cancer whose KRAS mutation happens to be the one that the first KRAS drugs were built for. Sotorasib and adagrasib, approved for lung cancer, shrink a share of these tumours after chemotherapy and are listed as options, and newer inhibitors such as elironrasib, olomorasib and the pan-RAS drug daraxonrasib are being tested in this group.
KRAS is mutated in more than nine out of ten pancreatic ductal adenocarcinomas, but the covalent inhibitors that reached the clinic first bind only the cysteine of the G12C variant, which is rare in the pancreas. The G12C subgroup otherwise resembles other KRAS-mutant pancreatic cancers in its presentation, its TP53, CDKN2A and SMAD4 co-alterations and its response to chemotherapy; it is found only by tumour or plasma sequencing, which is why guidelines ask for it at diagnosis in advanced disease.
Sotorasib in the pancreatic cohort of CodeBreaK 100 (2023) and adagrasib in KRYSTAL-1 (2023) produced responses in a minority of previously treated patients with disease control in most, durable for some months. Both are NCCN-listed options after first-line chemotherapy and are used off label or through access schemes, since neither has a pancreatic indication. Resistance arises through secondary KRAS mutations, amplification and bypass through receptor tyrosine kinases, and pancreatic tumours appear to depend more on wild-type RAS and on EGFR-family signalling than lung tumours do, which is the rationale for combining G12C inhibitors with EGFR antibodies or with pan-RAS drugs.
The pan-RAS inhibitor daraxonrasib, active against G12C alongside the other variants, lengthened survival in RASolute 302 and is approved after first-line chemotherapy regardless of KRAS subtype, so G12C-mutant patients now have a RAS inhibitor with pancreatic-specific evidence. Elironrasib (a RAS(ON) G12C-selective inhibitor) is being combined with daraxonrasib, olomorasib is in a pancreatic cohort, glecirasib has a pancreatic phase 2 in China, and divarasib, garsorasib and FMC-376 are in earlier studies. Open questions are whether a G12C-selective drug adds anything to a pan-RAS inhibitor, how to sequence them with chemotherapy, and whether responses in the pancreas can be made as deep as in the lung.
About 1 to 2 percent of pancreatic ductal adenocarcinomas carry KRAS G12C, far fewer than the G12D, G12V and G12R mutations that make up most of the rest, so it is a small group even in a common cancer.
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 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.
Nothing recorded yet.
Background: CA 19-9. Also on OnCo: Symptoms and red flags · Early detection roadmap.
Chemotherapy as for other pancreatic adenocarcinoma: modified FOLFIRINOX, NALIRIFOX or gemcitabine plus nab-paclitaxel; G12C inhibitors are not approved first line.
Daraxonrasib (RASolute 302, approved for pancreatic cancer irrespective of KRAS subtype); sotorasib or adagrasib as NCCN-listed options on the CodeBreaK 100 and KRYSTAL-1 cohorts.
Elironrasib with daraxonrasib, olomorasib, glecirasib and other G12C-selective inhibitors alone or with chemotherapy or EGFR antibodies.
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.
Sotorasib is a guideline-listed later-line option for the 1 to 2 percent of pancreatic cancers with KRAS G12C, and the proof that KRAS in pancreatic cancer is druggable; the larger opportunity lies with inhibitors of G12D and pan-RAS drugs.
Adagrasib joins sotorasib as a later-line option for KRAS G12C pancreatic cancer in guidelines; both drugs are the template for the G12D and pan-RAS inhibitors now in pancreatic trials.
Patients with KRAS G12C lung cancer that has progressed after chemo-immunotherapy can take an oral KRAS inhibitor instead of docetaxel and gain a somewhat longer time to progression with fewer severe side effects, but should understand that most tumours become resistant within a year and that survival is not improved. KRAS G12C testing is worthwhile, but first-generation inhibitors are a step rather than a cure; combinations and next-generation inhibitors are the active research fronts.
The most frequently mutated oncogene in cancer stopped being undruggable, and patients with KRAS G12C lung and bowel cancers now have targeted pills. The approach, exploiting a mutation-created chemical handle and an inactive-state pocket, has become a template for other hard targets.
Query for this cancer: (TITLE:"KRAS G12C-mutant pancreatic ductal adenocarcinoma" OR ABSTRACT:"KRAS G12C-mutant pancreatic ductal adenocarcinoma" OR TITLE:"KRAS G12C pancreatic cancer" OR ABSTRACT:"KRAS G12C pancreatic cancer" OR TITLE:"KRAS p.G12C PDAC" OR ABSTRACT:"KRAS p.G12C PDAC" OR TITLE:"G12C-mutant pancreatic adenocarcinoma" OR ABSTRACT:"G12C-mutant pancreatic adenocarcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about KRAS G12C-mutant 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.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
No adjustment for mild impairment; hepatotoxicity is common and worse after recent immunotherapy.
The three main regimens share low blood counts, tiredness, sickness and sore mouth; FOLFIRINOX and NALIRIFOX add irinotecan diarrhoea and oxaliplatin's cold-triggered tingling and rare throat spasm, gemcitabine with nab-paclitaxel adds hair loss and neuropathy, and every regimen comes with the same temperature rule for ringing the 24-hour line.
See all on the product pages:AdagrasibDaraxonrasibElironrasibFOLFIRINOX / mFOLFIRINOXGemcitabine + nab-paclitaxelNALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)OlomorasibSotorasib·Printable cards in the navigator
Newly diagnosed? Read the first 60 days with KRAS G12C-mutant 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.