The first 60 days: MET exon 14 and MET-amplified non-small-cell lung cancer
MET-driven lung cancer comes in three forms: an exon 14 skipping mutation treated with the pills capmatinib or tepotinib, MET amplification that often arises as an escape route from EGFR drugs, and high c-Met protein levels that the antibody-drug conjugate telisotuzumab vedotin targets. Below, week by week, is what OnCo's record of MET exon 14 and MET-amplified 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.
- 1.MET amplification after osimertinib in EGFR-mutated diseaseNCCN Guidelines: Non-Small Cell Lung Cancer
Osimertinib plus savolitinib (SAVANNAH, SACHI) where available; amivantamab plus chemotherapy; platinum-pemetrexed.
OsimertinibSavolitinibOsimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior OsimertinibAmivantamabA Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib FailureMET amplification (bypass resistance) Capmatinib (GEOMETRY mono-1) or tepotinib (VISION); platinum-pemetrexed with or without pembrolizumab if the inhibitor is not tolerated or after it.
Telisotuzumab vedotin (LUMINOSITY) after platinum chemotherapy; TeliMET NSCLC-01 versus docetaxel is confirmatory.
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 MET exon 14 skipping by RNA or DNA sequencing, MET gene copy number by fluorescence in situ hybridisation or sequencing, c-Met immunohistochemistry, MET amplification in plasma or tissue at progression on osimertinib, Peripheral oedema and creatinine on MET inhibitors), 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 MET exon 14 skipping adenocarcinoma or sarcomatoid carcinoma, De novo high-level MET amplification, MET amplification as acquired resistance in EGFR-mutated adenocarcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Advanced MET exon 14, first line or later
- For my situation (advanced met exon 14, first line or later), which of the standard options do you recommend and why?Guideline options include: Capmatinib (GEOMETRY mono-1) or tepotinib (VISION); platinum-pemetrexed with or without pembrolizumab if the inhibitor is not tolerated or after it.
- Am I a candidate for Capmatinib, Tepotinib, Capmatinib & tepotinib 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 GEOMETRY mono-1 and Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
MET amplification after osimertinib in EGFR-mutated disease
- For my situation (met amplification after osimertinib in egfr-mutated disease), which of the standard options do you recommend and why?Guideline options include: Osimertinib plus savolitinib (SAVANNAH, SACHI) where available; amivantamab plus chemotherapy; platinum-pemetrexed.
- Am I a candidate for Osimertinib, Savolitinib, Amivantamab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib and A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
c-Met overexpression, previously treated non-squamous
- For my situation (c-met overexpression, previously treated non-squamous), which of the standard options do you recommend and why?Guideline options include: Telisotuzumab vedotin (LUMINOSITY) after platinum chemotherapy; TeliMET NSCLC-01 versus docetaxel is confirmatory.
- Am I a candidate for Telisotuzumab vedotin, Docetaxel, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of LUMINOSITY and TeliMET NSCLC-01 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 TeliMET NSCLC-01, Telisotuzumab adizutecan, Savolitinib, Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib?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 “MET amplification has no agreed threshold and results differ between assays”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Peripheral oedema limits the dose of every MET inhibitor and has no good treatment”. 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 Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib FailurePhase 3 · active · NCT04988295A Phase 3, Open-Label, Randomized Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure
- TeliMET NSCLC-01Phase 3 · recruiting · NCT04928846Previously treated c-Met-overexpressing, EGFR-wild-type non-squamous NSCLC: telisotuzumab vedotin vs docetaxel
- Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior OsimertinibPhase 2 · active · NCT03778229A Phase II Study Assessing the Efficacy of Osimertinib in Combination With Savolitinib in Patients With EGFRm+ and MET+, Locally Advanced or Metastatic Non Small Cell Lung Cancer Who Have Progressed Following Treatment With Osimertinib.
- Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)Phase 2 · active · NCT02864992A Phase II Single-arm Trial to Investigate Tepotinib in Advanced (Locally Advanced or Metastatic) Non-small Cell Lung Cancer With METex14 Skipping Alterations or MET Amplification (VISION)
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- MET exon 14 and MET-amplified non-small-cell lung cancer: the full pageMET-driven lung cancer comes in three forms: an exon 14 skipping mutation treated with the pills capmatinib or tepotinib, MET amplification that often arises as an escape route from EGFR drugs, and high c-Met protein levels that the antibody-drug conjugate telisotuzumab vedotin targets.
- 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.
- MET amplification (bypass resistance): When lung cancer switches on the MET receptor to bypass a blocked EGFR pill.
- Driver mutation: One of the few mutations in a tumour that actually causes it to grow.
- Tyrosine kinase inhibitor (TKI): Pills that block the on-switch enzyme (a kinase) that a particular cancer depends on: imatinib for CML, osimertinib for EGFR lung cancer, ibrutinib for CLL.
- Drug resistance (primary and acquired): Why cancer drugs stop working: the tumour either never depended on the target or evolves around the block.
Every term links to the glossary.