The first 60 days: KRAS G12C-mutant pancreatic ductal adenocarcinoma
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. Below, week by week, is what OnCo's record of KRAS G12C-mutant 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.
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.
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: 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.
ElironrasibStudy of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid TumorsOlomorasibStudy of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)GlecirasibA Phase II Study Evaluating JAB-21822 Monotherapy in Adult Patients With Pancreatic Cancer and Other Solid Tumors Harboring the KRAS p.G12C Mutation.
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 G12C by tissue or plasma next-generation sequencing, Co-alterations in TP53, CDKN2A and SMAD4, Acquired KRAS mutations, KRAS amplification or receptor tyrosine kinase bypass at progression, CA 19-9 for response monitoring, Liver enzymes on a G12C inhibitor), 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 KRAS G12C PDAC after first-line chemotherapy, KRAS G12C PDAC in trials of G12C-selective inhibitors, KRAS G12C PDAC with acquired resistance.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
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: modified FOLFIRINOX, NALIRIFOX or gemcitabine plus nab-paclitaxel; G12C inhibitors are not approved first line.
- 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.
After first-line chemotherapy
- For my situation (after first-line chemotherapy), which of the standard options do you recommend and why?Guideline options include: 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.
- Am I a candidate for Daraxonrasib, Sotorasib, Adagrasib, 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.
Clinical trials
- For my situation (clinical trials), which of the standard options do you recommend and why?Guideline options include: Elironrasib with daraxonrasib, olomorasib, glecirasib and other G12C-selective inhibitors alone or with chemotherapy or EGFR antibodies.
- Am I a candidate for Elironrasib, Olomorasib, Glecirasib, 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 Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors and Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C) 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 Elironrasib, Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors, Olomorasib, Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)?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 “Responses to G12C-selective inhibitors are shallower and shorter in the pancreas than in the lung”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Neither sotorasib nor adagrasib has a pancreatic indication, so access depends on off-label use and trials”. 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.
- 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
- A Phase II Study Evaluating JAB-21822 Monotherapy in Adult Patients With Pancreatic Cancer and Other Solid Tumors Harboring the KRAS p.G12C Mutation.Phase 2 · recruiting · NCT06008288A Single-arm, Multicenter, Open-label Phase II Clinical Study Evaluating the Efficacy and Safety of JAB-21822 Monotherapy in Patients With Locally Advanced or Metastatic Pancreatic Cancer and Other Solid Tumors Harboring the KRAS p.G12C Mutation.
- A Study Evaluating FMC-376 in Participants With KRAS G12C Mutated Solid TumorsPhase 1/2 · recruiting · NCT06244771An Open-Label, Phase 1/2 Dose Escalation, Dose Expansion and Cohort Expansion Study Evaluating the Safety, PK and Clinical Activity of FMC-376 in Participants With KRAS G12C Mutated Locally Advanced Unresectable or Metastatic Solid Tumors
- Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid TumorsPhase 1/2 · recruiting · NCT06128551Phase 1b/2, Multicenter, Open-label, Dose Escalation and Dose Expansion Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Patients With Advanced KRAS G12C-Mutated Solid Tumors
- Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)Phase 1/2 · active · NCT04956640A Phase 1/2 Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors
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 G12C-mutant pancreatic ductal adenocarcinoma: the full pageKRAS 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.
- 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.
- Oncogene: A gene that, when over-activated by mutation or extra copies, pushes a cell to grow and divide.
- KRAS mutation subtypes (G12C, G12D, G12V): KRAS, the most commonly mutated cancer gene, comes in flavours named by the exact amino acid change.
- 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.
- Driver mutation: One of the few mutations in a tumour that actually causes it to grow.
Every term links to the glossary.