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MET exon 14 and MET-amplified non-small-cell lung cancer: the decisions you may face

3 treatment settings, 3 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.

Advanced, first line

Advanced MET exon 14, first line or later

Capmatinib (GEOMETRY mono-1) or tepotinib (VISION); platinum-pemetrexed with or without pembrolizumab if the inhibitor is not tolerated or after it.

The options, in plain words

Capmatinib is a targeted pill for the small group of lung cancers driven by a MET exon 14 skipping mutation, found by tumour sequencing.

Tepotinib is a once-daily targeted pill for lung cancers driven by a MET exon 14 skipping mutation, and the MET inhibitor NICE funds in England.

Capmatinib and tepotinib are two pills for the roughly 3% of lung cancers with a MET exon 14 skipping mutation.

Pemetrexed is the chemotherapy that, with a platinum drug, became the first approved treatment for mesothelioma in 2004, and is still the backbone today.

Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.

The evidence behind it
  • Advanced non-small-cell lung cancer with MET exon 14 skipping or MET amplification: capmatinib monotherapy in cohorts by prior treatment and MET gene copy number

    Response rate 68% (treatment-naive, n=28) and 41% (previously treated, n=69) in MET exon 14 skipping disease; about a third in high-level MET amplification.

    Objective response rate, MET exon 14 skipping (%): Treatment-naive 68 (n=28) vs Previously treated 41 (n=69) · source
  • Tests Tepotinib
    A 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)

    No headline result recorded yet.

The main trade-offs on record
  • Capmatinib: photosensitivity, use sun protection. Tepotinib: take with food.
  • Not recommended for CrCl below 45.
  • Dose by Calvert formula using GFR (see the calculators).
Questions to ask about this decision
  1. Between Capmatinib, Tepotinib, Capmatinib & tepotinib and the other options, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in GEOMETRY mono-1 and Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION), and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. For my situation (advanced met exon 14, first line or later), which of the standard options do you recommend and why?
    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.
  7. Am I a candidate for Capmatinib, Tepotinib, Capmatinib & tepotinib or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  8. How do the results of GEOMETRY mono-1 and Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

MET amplification after osimertinib in EGFR-mutated disease

Osimertinib plus savolitinib (SAVANNAH, SACHI) where available; amivantamab plus chemotherapy; platinum-pemetrexed.

The options, in plain words

Osimertinib (Tagrisso) is the standard pill for EGFR-mutant lung cancer, now also given after surgery and with chemotherapy or after chemoradiation.

Savolitinib is a Chinese-discovered pill that blocks the MET growth signal, approved in China for lung cancers with a MET exon 14 mutation and being tested worldwide with osimertinib.

A two-armed antibody that blocks EGFR and its escape partner MET, now first-line for EGFR-mutant lung cancer with lazertinib.

The evidence behind it
The main trade-offs on record
Side effectAny gradeGrade 3+
Decreased appetite · FLAURA20%2.5%
Diarrhoea · FLAURA58%2.2%
Fatigue · FLAURA21%1.4%
Rash · FLAURA58%1.1%
  • Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
  • No adjustment for mild or moderate impairment; not studied in severe.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Side effectAny gradeGrade 3+
Rash · MARIPOSA, with lazertinib86%26%
Nail toxicity · MARIPOSA, with lazertinib71%11%
Venous thromboembolism · MARIPOSA, with lazertinib36%11%
Infusion-related reaction · MARIPOSA, with lazertinib63%6%
  • No food effect (intravenous or subcutaneous antibody).

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Questions to ask about this decision
  1. Between Osimertinib, Savolitinib and Amivantamab, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in 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, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. Which side effects of Osimertinib or Amivantamab are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  5. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  6. Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  7. For my situation (met amplification after osimertinib in egfr-mutated disease), which of the standard options do you recommend and why?
    Why: Guideline options include: Osimertinib plus savolitinib (SAVANNAH, SACHI) where available; amivantamab plus chemotherapy; platinum-pemetrexed.
  8. Am I a candidate for Osimertinib, Savolitinib, Amivantamab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  9. 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?
    Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

c-Met overexpression, previously treated non-squamous

Telisotuzumab vedotin (LUMINOSITY) after platinum chemotherapy; TeliMET NSCLC-01 versus docetaxel is confirmatory.

The options, in plain words

Telisotuzumab vedotin (Emrelis) is the first c-MET-directed ADC, approved in 2025 for lung cancer with high c-MET protein.

The first chemotherapy to extend life in prostate cancer (2004), now part of triplet therapy at first metastatic diagnosis.

The evidence behind it
The main trade-offs on record
  • Do not give if bilirubin above ULN, or AST/ALT above 1.5 x ULN with alkaline phosphatase above 2.5 x ULN (treatment-related deaths).
Questions to ask about this decision
  1. Between Telisotuzumab vedotin and Docetaxel, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in LUMINOSITY and TeliMET NSCLC-01, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. For my situation (c-met overexpression, previously treated non-squamous), which of the standard options do you recommend and why?
    Why: Guideline options include: Telisotuzumab vedotin (LUMINOSITY) after platinum chemotherapy; TeliMET NSCLC-01 versus docetaxel is confirmatory.
  7. Am I a candidate for Telisotuzumab vedotin, Docetaxel, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  8. How do the results of LUMINOSITY and TeliMET NSCLC-01 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.