The first 60 days: Metastatic pancreatic ductal adenocarcinoma
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. Below, week by week, is what OnCo's record of Metastatic 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.
Weeks 1 to 2
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Biomarkers your report may list
KRAS mutation subtype by tissue or plasma sequencing (G12D, G12V, G12R, G12C; wild-type prompts fusion testing)Germline BRCA1, BRCA2, PALB2 and ATM (platinum and PARP inhibitor choice)Mismatch repair status by immunohistochemistry or sequencing (pembrolizumab)NRG1, NTRK, ALK, ROS1, FGFR2 and RET fusions and BRAF alterations in KRAS wild-type tumoursCA 19-9 for response monitoring (uninformative in Lewis-negative patients)Claudin 18.2 and mesothelin expression (trial eligibility)Performance status, bilirubin and neuropathy (regimen choice)
Ask which of these were tested and what the results were; see the report reader for what each value means.
Tests and imaging linked to this cancer
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: Maintenance and biomarker-directed therapy, Clinical trials.
- SurgeonNamed in the standard of care for: Supportive care throughout.
- Medical oncologistNamed in the standard of care for: First line, fit patients, First line, less fit patients, Maintenance and biomarker-directed therapy, Second line and 1 more.
- Transplant and cell therapy teamNamed in the standard of care for: Clinical trials.
- Palliative and supportive care teamNamed in the standard of care for: First line, less fit patients, Supportive care throughout.
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.
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.
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.
Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic AdenocarcinomaZoldonrasibStudy of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-MutELI-002 7PA Multicenter Study of IBI343 Monotherapy Versus Placebo in Subjects With Previously Treated, Claudin (CLDN) 18.2-positive, Pancreatic Cancer(G-HOPE-002)Claudin18.2 CAR-T (CT041) in Patients With Gastric, Pancreatic Cancer, or Other Specified Digestive CancersPrecision PromiseDaraxonrasib after first-line chemotherapy (RASolute 302); otherwise switch backbone, liposomal irinotecan with fluorouracil after gemcitabine or a gemcitabine-based regimen after FOLFIRINOX.
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.
Biliary stenting, pancreatic enzyme replacement, dietetic support, early palliative care, anticoagulation for thrombosis and coeliac plexus block for pain.
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 mutation subtype by tissue or plasma sequencing, Germline BRCA1, BRCA2, PALB2 and ATM, Mismatch repair status by immunohistochemistry or sequencing, NRG1, NTRK, ALK, ROS1, FGFR2 and RET fusions and BRAF alterations in KRAS wild-type tumours, CA 19-9 for response monitoring), 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 Metastatic PDAC, fit for combination chemotherapy, Metastatic PDAC, unfit for combination chemotherapy, Metastatic PDAC with a KRAS G12D, G12V or G12R mutation.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
First line, fit patients
- For my situation (first line, fit patients), which of the standard options do you recommend and why?Guideline options include: Modified FOLFIRINOX or NALIRIFOX (NAPOLI 3); gemcitabine plus nab-paclitaxel as the alternative, chosen by fitness, biliary drainage and neuropathy.
- 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.
- How do the results of NAPOLI 3 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
First line, less fit patients
- For my situation (first line, less fit patients), which of the standard options do you recommend and why?Guideline options include: Gemcitabine plus nab-paclitaxel at reduced dose or gemcitabine alone; best supportive care when chemotherapy would do harm.
- Am I a candidate for Gemcitabine + nab-paclitaxel, Gemcitabine, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Maintenance and biomarker-directed therapy
- For my situation (maintenance and biomarker-directed therapy), which of the standard options do you recommend and why?Guideline options include: 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.
- Am I a candidate for Olaparib, Pembrolizumab, Zenocutuzumab or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of POLO apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Second line
- For my situation (second line), which of the standard options do you recommend and why?Guideline options include: Daraxonrasib after first-line chemotherapy (RASolute 302); otherwise switch backbone, liposomal irinotecan with fluorouracil after gemcitabine or a gemcitabine-based regimen after FOLFIRINOX.
- Am I a candidate for Daraxonrasib, Irinotecan (and liposomal irinotecan), Fluorouracil (5-FU) or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of RASolute 302 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Supportive care throughout
- For my situation (supportive care throughout), which of the standard options do you recommend and why?Guideline options include: Biliary stenting, pancreatic enzyme replacement, dietetic support, early palliative care, anticoagulation for thrombosis and coeliac plexus block for pain.
Clinical trials
- For my situation (clinical trials), which of the standard options do you recommend and why?Guideline options include: 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.
- Am I a candidate for Zoldonrasib, ELI-002 7P, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma and Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mut 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 Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma, Zoldonrasib, Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mut, Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-muta?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 “Resistance to RAS inhibitors emerges within months and the best partner drugs are unknown”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Checkpoint inhibitors fail outside mismatch repair deficient disease because the tumour excludes T cells”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Multicenter Study of IBI343 Monotherapy Versus Placebo in Subjects With Previously Treated, Claudin (CLDN) 18.2-positive, Pancreatic Cancer(G-HOPE-002)Phase 3 · recruiting · NCT07066098A Multicenter, Randomized, Double-Blind, Phase III Study of IBI343 Monotherapy Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Participants With Claudin (CLDN) 18.2-Positive, Locally Advanced Unresectable or Metastatic Pancreatic Cancer Who Received>=2 Prior Lines of Therapy
- A Study to Evaluate Chemotherapy With or Without INCB161734 in Previously Untreated, KRAS G12D-Mutated Metastatic Pancreatic Ductal AdenocarcinomaPhase 3 · recruiting · NCT07522073A Randomized, Double-Blind, Phase 3 Study of Chemotherapy With or Without INCB161734 in Previously Untreated, KRAS G12D-Mutated Metastatic Pancreatic Ductal Adenocarcinoma (DAWN-303)
- Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic AdenocarcinomaPhase 3 · recruiting · NCT07562152A Phase 3 Randomized, Open-Label Study of Atebimetinib in Combination With the Modified Gemcitabine and Nab-Paclitaxel Regimen Versus the Standard Gemcitabine and Nab-Paclitaxel Regimen for the Treatment of Patients With Metastatic Pancreatic Ductal Pancreatic Adenocarcinoma Cancer (MAPKeeper 301)
- Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic AdenocarcinomaPhase 3 · recruiting · NCT07491445RASolute 303: A Phase 3 Global, Multicenter, Open-label, Randomized, 3-Arm Study of Daraxonrasib Monotherapy or Daraxonrasib Plus Gemcitabine and Nab-paclitaxel Versus Gemcitabine and Nab-paclitaxel as a First-Line Treatment for Patients With Metastatic Pancreatic Adenocarcinoma
- Study of Quemliclustat and Chemotherapy Versus Placebo and Chemotherapy in Patients With Metastatic Pancreatic Ductal AdenocarcinomaPhase 3 · active · NCT06608927A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase 3 Trial of Quemliclustat and Chemotherapy Versus Placebo and Chemotherapy in Patients With Treatment-Naive Metastatic Pancreatic Ductal Adenocarcinoma
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Metastatic pancreatic ductal adenocarcinoma: the full pageMetastatic 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.
- 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.
Words this page and the cancer page use
- Metastasis: Cancer that has spread from where it started to distant parts of the body, travelling through the blood or lymph.
- Cancer cachexia: Severe loss of weight and muscle in advanced cancer that eating more cannot reverse on its own.
- Platinum-sensitive / platinum-resistant: Whether a cancer that responded to platinum chemotherapy came back more than six months later (sensitive, so platinum can be used again) or sooner (resistant, so something else is needed).
- KRAS mutation subtypes (G12C, G12D, G12V): KRAS, the most commonly mutated cancer gene, comes in flavours named by the exact amino acid change.
- Obstructive jaundice and biliary obstruction: Yellowing of the skin and eyes because a tumour blocks the bile duct, most often pancreatic or bile duct cancer.
- Peritoneal metastasis: Spread across the lining of the abdomen, the most common way stomach cancer recurs and the hardest to treat.
- Germline BRCA mutation (gBRCA): An inherited fault in the BRCA1 or BRCA2 gene, present in every cell from birth, that greatly raises the risk of breast, ovarian, prostate and pancreatic cancer and makes those cancers sensitive to PARP inhibitors and platinum.
- CA 19-9: A sugar molecule shed into the blood by most pancreatic cancers; useful to follow treatment, not to screen.
- 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.
Every term links to the glossary.