The first 60 days: KRAS G12C-mutant colorectal cancer
KRAS G12C bowel cancer carries a mutation that was undruggable for forty years. The first KRAS drugs work only weakly on their own in the bowel, because the tumour switches EGFR back on, so they are given with an anti-EGFR antibody: sotorasib with panitumumab and adagrasib with cetuximab are both approved after chemotherapy. Below, week by week, is what OnCo's record of KRAS G12C-mutant colorectal cancer 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.
FOLFOX, FOLFIRI or CAPOX with bevacizumab, as for any RAS-mutant colorectal cancer; anti-EGFR antibodies are not used; KRAS G12C combinations are under test first line (CodeBreaK 301).
Sotorasib plus panitumumab (CodeBreaK 300) or adagrasib plus cetuximab (KRYSTAL-1) after fluoropyrimidine, oxaliplatin and irinotecan.
Trifluridine-tipiracil with bevacizumab (SUNLIGHT), fruquintinib (FRESCO-2) or regorafenib; clinical trials of next-generation RAS inhibitors.
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 tumour or circulating tumour DNA sequencing, Extended RAS testingbefore any anti-EGFR antibody, Co-mutationsand acquired RAS or MAPK alterations at progression, Mismatch repair status), 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 with an anti-EGFR combination, Other KRAS mutations: RASand pan-RAS inhibitors in trials, RAS-mutant colorectal cancer, left-sided or right-sided, in which anti-EGFR antibodies do not work.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Metastatic, previously treated
- For my situation (metastatic, previously treated), which of the standard options do you recommend and why?Guideline options include: Sotorasib plus panitumumab (CodeBreaK 300) or adagrasib plus cetuximab (KRYSTAL-1) after fluoropyrimidine, oxaliplatin and irinotecan.
- Am I a candidate for Sotorasib, Panitumumab, Adagrasib 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 CodeBreaK 300 and Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, first line
- For my situation (metastatic, first line), which of the standard options do you recommend and why?Guideline options include: FOLFOX, FOLFIRI or CAPOX with bevacizumab, as for any RAS-mutant colorectal cancer; anti-EGFR antibodies are not used; KRAS G12C combinations are under test first line (CodeBreaK 301).
- Am I a candidate for FOLFOX (5-FU, leucovorin, oxaliplatin), FOLFIRI (5-FU, leucovorin, irinotecan), CAPOX (capecitabine, oxaliplatin) 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 Study of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb in Treatment-naïve Participants With Metastatic Colorectal apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Later lines
- For my situation (later lines), which of the standard options do you recommend and why?Guideline options include: Trifluridine-tipiracil with bevacizumab (SUNLIGHT), fruquintinib (FRESCO-2) or regorafenib; clinical trials of next-generation RAS inhibitors.
- Am I a candidate for Trifluridine/tipiracil, Fruquintinib, Regorafenib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of SUNLIGHT and FRESCO-2 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 Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb in Treatment-naïve Participants With Metastatic Colorectal, Phase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10), Divarasib, Olomorasib?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 last months, not years; acquired RAS and MAPK alterations drive resistance”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “G12D, the commonest colorectal KRAS allele, has no approved drug”. 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.
- Phase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10)Phase 3 · active · NCT04793958A Randomized Phase 3 Study of MRTX849 in Combination With Cetuximab Versus Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation With Disease Progression On or After Standard First-Line Therapy
- Study of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb in Treatment-naïve Participants With Metastatic ColorectalPhase 3 · recruiting · NCT06252649Phase 3 Multicenter, Randomized, Open-label, Active-controlled Study of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb for Treatment-naïve Subjects With Metastatic Colorectal Cancer With KRAS p.G12C Mutation (CodeBreaK 301)
- A Study of GFH375 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors Harboring KRAS G12D MutationPhase 1/2 · recruiting · NCT07259590A Multicenter, Open-Label, Phase Ib/II Clinical Study to Explore the Efficacy, Pharmacokinetics and Safety/Tolerability of GFH375 in Combination With Cetuximab or Chemotherapy in Participants With Advanced Solid Tumors Harboring KRAS G12D Mutation
- JAB-21822 in Combination With Cetuximab in Patients With Advanced CRC and Other Solid Tumors With KRAS G12C MutationPhase 1/2 · active · NCT05194995A Phase Ib/II Trial of JAB-21822 in Combination With Cetuximab in Patients With Advanced Colorectal Cancer, Small Intestine Cancer and Appendiceal Cancer With KRAS G12C Mutation
- Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1Phase 1/2 · active · NCT03785249A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1
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 colorectal cancer: the full pageKRAS G12C bowel cancer carries a mutation that was undruggable for forty years. The first KRAS drugs work only weakly on their own in the bowel, because the tumour switches EGFR back on, so they are given with an anti-EGFR antibody: sotorasib with panitumumab and adagrasib with cetuximab are both approved after chemotherapy.
- 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.
- Next-generation sequencing (NGS): Reading millions of DNA fragments in parallel, the engine behind every modern genomic test.
- Sidedness (left vs right colon): Where in the colon a tumour starts changes its biology and which drugs work.
- Circulating tumour DNA (ctDNA): Circulating tumour DNA (ctDNA) consists of fragments of DNA shed by tumour cells into the blood, detectable with sensitive sequencing.
Every term links to the glossary.