The first 60 days: KRAS wild-type pancreatic ductal adenocarcinoma
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. Below, week by week, is what OnCo's record of KRAS wild-type pancreatic ductal adenocarcinoma says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
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.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Diagnosis, First line, NTRK fusion.
- Medical oncologistNamed in the standard of care for: First line, NRG1 fusion, NTRK fusion, BRAF alteration and 2 more.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
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.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example KRAS wild-type status on tumour or plasma sequencing, RNA-based or comprehensive fusion testing for NRG1, NTRK, ALK, ROS1, FGFR2, RET, MET and BRAF fusions, BRAF V600E and in-frame deletion status, Mismatch repair immunohistochemistry or microsatellite instability testing, ERBB2 amplification and GNAS mutation), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include NRG1 fusion-positive KRAS wild-type PDAC, NTRK fusion-positive KRAS wild-type PDAC, BRAF V600E-mutant or BRAF in-frame deletion KRAS wild-type PDAC.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Diagnosis
- For my situation (diagnosis), which of the standard options do you recommend and why?Guideline options include: 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.
First line
- For my situation (first line), which of the standard options do you recommend and why?Guideline options include: 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.
- Am I a candidate for FOLFIRINOX / mFOLFIRINOX, NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV), Gemcitabine + nab-paclitaxel, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
NRG1 fusion
- For my situation (nrg1 fusion), which of the standard options do you recommend and why?Guideline options include: Zenocutuzumab (eNRGy), approved December 2024 for pancreatic cancer with an NRG1 fusion after prior systemic therapy.
- Am I a candidate for Zenocutuzumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
NTRK fusion
- For my situation (ntrk fusion), which of the standard options do you recommend and why?Guideline options include: Larotrectinib or entrectinib, approved for NTRK fusion-positive solid tumours; repotrectinib after resistance.
- Am I a candidate for Larotrectinib, Entrectinib, Repotrectinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
BRAF alteration
- For my situation (braf alteration), which of the standard options do you recommend and why?Guideline options include: Dabrafenib plus trametinib for BRAF V600E (tumour-agnostic approval); MEK inhibitors for BRAF in-frame deletions on case-series evidence.
- Am I a candidate for Dabrafenib + trametinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Other fusions
- For my situation (other fusions), which of the standard options do you recommend and why?Guideline options include: ALK, ROS1, RET and FGFR2 inhibitors extrapolated from other cancers; mismatch repair deficient tumours receive pembrolizumab.
- Am I a candidate for Repotrectinib, Pembrolizumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
No identified driver
- For my situation (no identified driver), which of the standard options do you recommend and why?Guideline options include: Chemotherapy; nimotuzumab plus gemcitabine approved in China after NOTABLE.
- Am I a candidate for Nimotuzumab, Gemcitabine, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of NOTABLE (nimotuzumab, KRAS wild-type pancreatic cancer) apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Zenocutuzumab, Repotrectinib, Nimotuzumab, NOTABLE (nimotuzumab, KRAS wild-type pancreatic cancer)?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “Fusion testing is still missed when DNA panels are used alone, so many actionable tumours go unrecognised”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Each driver is too rare for pancreatic-specific randomised trials; evidence is extrapolated from lung cancer and basket studies”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- KRAS wild-type pancreatic ductal adenocarcinoma: the full pageKRAS 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.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- KRAS mutation subtypes (G12C, G12D, G12V): KRAS, the most commonly mutated cancer gene, comes in flavours named by the exact amino acid change.
- BRAF V600E mutation: A single spelling change in the BRAF gene that jams a growth switch permanently on.
- Drug resistance (primary and acquired): Why cancer drugs stop working: the tumour either never depended on the target or evolves around the block.
- Gene fusion: A gene fusion is two genes broken and joined together, creating a hybrid protein that can drive cancer.
- Driver mutation: One of the few mutations in a tumour that actually causes it to grow.
- Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR): Microsatellite instability is the mark of a broken DNA spell-checker (loss of MLH1, MSH2, MSH6 or PMS2) that leaves thousands of mutations, so the tumour displays abnormal proteins that T cells can recognise.
Every term links to the glossary.