The first 60 days: KRAS G12C-mutant non-small-cell lung cancer
KRAS G12C lung cancer carries a mutation that was thought impossible to drug for forty years. Sotorasib and adagrasib now shrink about four in ten tumours after chemotherapy and immunotherapy, though the benefit is measured in months, and newer inhibitors and first-line combinations with immunotherapy are in trials. Below, week by week, is what OnCo's record of KRAS G12C-mutant non-small-cell lung 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.
As for driver-negative disease: pembrolizumab plus platinum doublet, or pembrolizumab alone if PD-L1 is 50 percent or more; KRAS inhibitors are not yet approved first line.
Sotorasib (CodeBreaK 200) or adagrasib (KRYSTAL-12), preferred to docetaxel; adagrasib for active brain metastases; docetaxel with or without ramucirumab afterwards.
Divarasib versus sotorasib or adagrasib (Krascendo 1); olomorasib or adagrasib with pembrolizumab first line (SUNRAY-01, KRYSTAL-7); pan-RAS inhibitors.
DivarasibKrascendo 1OlomorasibA Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung CancerPhase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS GDaraxonrasib
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 sequencing, PD-L1 tumour proportion score, STK11 and KEAP1 co-mutations, TP53 co-mutation, Acquired KRAS mutations, MET amplification or bypass alterations at progression), 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 adenocarcinoma with high PD-L1, KRAS G12C adenocarcinoma with STK11 or KEAP1 co-mutation, KRAS G12C with brain metastases.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and why?Guideline options include: As for driver-negative disease: pembrolizumab plus platinum doublet, or pembrolizumab alone if PD-L1 is 50 percent or more; KRAS inhibitors are not yet approved first line.
- Am I a candidate for Pembrolizumab, Carboplatin, Pemetrexed 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 KEYNOTE-024 & KEYNOTE-189 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Advanced, after chemoimmunotherapy
- For my situation (advanced, after chemoimmunotherapy), which of the standard options do you recommend and why?Guideline options include: Sotorasib (CodeBreaK 200) or adagrasib (KRYSTAL-12), preferred to docetaxel; adagrasib for active brain metastases; docetaxel with or without ramucirumab afterwards.
- Am I a candidate for Sotorasib, Adagrasib, Docetaxel 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 200 and KRYSTAL-12 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Advanced, clinical trials
- For my situation (advanced, clinical trials), which of the standard options do you recommend and why?Guideline options include: Divarasib versus sotorasib or adagrasib (Krascendo 1); olomorasib or adagrasib with pembrolizumab first line (SUNRAY-01, KRYSTAL-7); pan-RAS inhibitors.
- Am I a candidate for Divarasib, Olomorasib, Daraxonrasib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Krascendo 1 and A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung 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 Divarasib, Krascendo 1, Olomorasib, A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung 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 “Responses to G12C inhibitors are shallower and shorter in lung cancer than EGFR or ALK inhibitors achieve, and no overall survival benefit over docetaxel has been shown”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Liver toxicity when a G12C inhibitor follows or accompanies a checkpoint inhibitor limits first-line combinations”. 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 Clinical Study of Calderasib (MK-1084) and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007)Phase 3 · recruiting · NCT07190248A Phase 3, Randomized, Open-label, Multicenter Clinical Study to Evaluate the Safety and Efficacy of MK-1084 in Combination With Subcutaneous Pembrolizumab and Berahyaluronidase Alfa (MK-3475A) Versus MK-3475A in Combination With Pemetrexed/Platinum (Carboplatin or Cisplatin) Chemotherapy as First-line Treatment of Participants With KRAS G12C-Mutant, Advanced or Metastatic Nonsquamous NSCLC (KANDLELIT-007)
- A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung CancerPhase 3 · recruiting · NCT06119581SUNRAY-01, A Global Pivotal Study in Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Comparing First-Line Treatment of LY3537982 and Pembrolizumab vs Placebo and Pembrolizumab in Those With PD-L1 Expression ≥50% or LY3537982 and Pembrolizumab, Pemetrexed, Platinum vs Placebo and Pembrolizumab, Pemetrexed, Platinum Regardless of PD-L1 Expression
- Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS GPhase 2/3 · recruiting · NCT04613596A Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation
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 non-small-cell lung cancer: the full pageKRAS G12C lung cancer carries a mutation that was thought impossible to drug for forty years. Sotorasib and adagrasib now shrink about four in ten tumours after chemotherapy and immunotherapy, though the benefit is measured in months, and newer inhibitors and first-line combinations with immunotherapy are in trials.
- 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.
- Hepatotoxicity (liver enzyme elevation): Liver injury from a drug, usually detected as a rise in liver enzymes (ALT, AST) on routine blood tests before symptoms appear.
- Tumour proportion score (TPS): The PD-L1 score used in lung cancer: the percentage of tumour cells that stain positive.
- KRAS mutation subtypes (G12C, G12D, G12V): KRAS, the most commonly mutated cancer gene, comes in flavours named by the exact amino acid change.
- Driver mutation: One of the few mutations in a tumour that actually causes it to grow.
- Drug resistance (primary and acquired): Why cancer drugs stop working: the tumour either never depended on the target or evolves around the block.
- Brain metastases (intracranial disease): Tumour deposits that have travelled to the brain from a cancer elsewhere, ten times more common than cancers that start in the brain, mostly from lung, breast, melanoma and kidney cancer.
Every term links to the glossary.