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EGFR-mutated non-small-cell lung cancer: the decisions you may face

6 treatment settings, 5 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, first line (exon 19 deletion or L858R)

Osimertinib alone (FLAURA), osimertinib plus platinum-pemetrexed (FLAURA2) for patients with high burden or brain metastases who can take chemotherapy, or amivantamab plus lazertinib (MARIPOSA) with prophylaxis against rash and clots.

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.

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

A third-generation EGFR pill used together with amivantamab as the first regimen to beat osimertinib in EGFR-mutant lung cancer.

The evidence behind it
  • Untreated advanced non-small-cell lung cancer with an EGFR exon 19 deletion or L858R mutation: osimertinib versus gefitinib or erlotinib
    Show survival figures (1)

    Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

    • Median progression-free survival 18.9 vs 10.2 months (hazard ratio 0.46); median overall survival 38.6 vs 31.8 months (hazard ratio 0.80).
    Progression-free survival (months): Osimertinib 18.9 (n=279) vs Gefitinib or erlotinib 10.2 (n=277) · HR 0.46 · source
  • First-line EGFR-mutant NSCLC: osimertinib + chemotherapy vs osimertinib

    PFS HR 0.62; OS HR 0.77.

    Progression-free survival (investigator) (months): Osimertinib + chemotherapy 25.5 (n=279) vs Osimertinib 16.7 (n=278) · HR 0.62 · source
  • First-line EGFR-mutant NSCLC: amivantamab + lazertinib vs osimertinib

    PFS HR 0.70; OS HR 0.75.

    Progression-free survival (BICR) (months): Amivantamab + lazertinib 23.7 (n=429) vs Osimertinib 16.6 (n=429) · HR 0.7 · source
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, Amivantamab and Lazertinib, 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 FLAURA and FLAURA2, 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 (advanced, first line (exon 19 deletion or l858r)), which of the standard options do you recommend and why?
    Why: Guideline options include: Osimertinib alone (FLAURA), osimertinib plus platinum-pemetrexed (FLAURA2) for patients with high burden or brain metastases who can take chemotherapy, or amivantamab plus lazertinib (MARIPOSA) with prophylaxis against rash and clots.
  8. Am I a candidate for Osimertinib, Amivantamab, Lazertinib, 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 FLAURA and FLAURA2 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.

Advanced, first line

Advanced, exon 20 insertion

Amivantamab plus carboplatin-pemetrexed first line (PAPILLON); sunvozertinib after platinum chemotherapy.

The options, in plain words

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

An oral drug for EGFR exon 20 insertion lung cancer that succeeded where mobocertinib failed; approved in China (2023) and the US (2025).

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

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

Also referenced:EGFR exon 20 insertion
The evidence behind it
The main trade-offs on record
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.

  • Dose by Calvert formula using GFR (see the calculators).
  • Not recommended for CrCl below 45.
Questions to ask about this decision
  1. Between Amivantamab, Sunvozertinib, Carboplatin 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 A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions and Assessing an Oral EGFR Inhibitor, Sunvozertinib in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR or HER2 Mutation (WU-KONG1), 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 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 (advanced, exon 20 insertion), which of the standard options do you recommend and why?
    Why: Guideline options include: Amivantamab plus carboplatin-pemetrexed first line (PAPILLON); sunvozertinib after platinum chemotherapy.
  8. Am I a candidate for Amivantamab, Sunvozertinib, Carboplatin or related drugs, 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 A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions and Assessing an Oral EGFR Inhibitor, Sunvozertinib in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR or HER2 Mutation (WU-KONG1) 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.

Advanced, first line

Advanced, after osimertinib

Biopsy or plasma test for the mechanism: osimertinib plus savolitinib for MET amplification; otherwise amivantamab plus platinum chemotherapy (MARIPOSA-2), platinum-pemetrexed, or datopotamab deruxtecan after chemotherapy; platinum-etoposide for small-cell transformation.

The options, in plain words

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

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.

Datopotamab deruxtecan (Datroway) is the second TROP2 ADC and shares Enhertu's payload. In 2026 it became a first-line option for triple-negative breast cancer patients who cannot receive immunotherapy.

Platinum plus etoposide has been the chemotherapy backbone of small-cell lung cancer for over 40 years, and is now given with immunotherapy.

The evidence behind it
The main trade-offs on record
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.

Side effectAny gradeGrade 3+
Stomatitis · TROPION-Breast01, n=36059%7%
Fatigue · TROPION-Breast01, n=36044%4.2%
Nausea · TROPION-Breast01, n=36056%1.4%
Keratitis · TROPION-Breast01, n=36024%1.1%

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 Amivantamab, Savolitinib, Datopotamab deruxtecan 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 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 Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib, 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 Amivantamab or Datopotamab deruxtecan 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 (advanced, after osimertinib), which of the standard options do you recommend and why?
    Why: Guideline options include: Biopsy or plasma test for the mechanism: osimertinib plus savolitinib for MET amplification; otherwise amivantamab plus platinum chemotherapy (MARIPOSA-2), platinum-pemetrexed, or datopotamab deruxtecan after chemotherapy; platinum-etoposide for small-cell transformation.
  8. Am I a candidate for Amivantamab, Savolitinib, Datopotamab deruxtecan or related drugs, 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 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 Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib 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

Resected stage IB to IIIA

One path named

Surgery, adjuvant platinum chemotherapy where indicated, then three years of osimertinib (ADAURA).

The path, 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.

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.

Questions to ask about this decision
  1. Is Osimertinib the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?
    Why: A single standard does not mean a single choice; timing and trials are decisions too.
  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 ADAURA, 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 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 (resected stage ib to iiia), which of the standard options do you recommend and why?
    Why: Guideline options include: Surgery, adjuvant platinum chemotherapy where indicated, then three years of osimertinib (ADAURA).
  8. Am I a candidate for Osimertinib, 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 ADAURA 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.

Locally advanced

Unresectable stage III

2 options

Concurrent platinum chemoradiation followed by osimertinib until progression (LAURA) rather than durvalumab.

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.

IMRT and IGRT shape the radiation beam to the tumour's outline from multiple angles and check the patient's position with a scan before every session, so surrounding organs receive less dose. Fewer, larger doses are now standard in breast and prostate cancer, but a low-dose bath still spreads across normal tissue.

  • Conformal dose, fewer side effects
  • Hypofractionation saves visits
The evidence behind it
  • Unresectable stage III EGFR-mutant NSCLC after chemoradiation: osimertinib until progression vs placebo

    PFS HR 0.16.

    Progression-free survival (BICR) (months): Osimertinib 39.1 (n=143) vs Placebo 5.6 (n=73) · HR 0.16 · source
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.

  • Low-dose bath to normal tissue
  • Motion management
Questions to ask about this decision
  1. Between Osimertinib and IMRT / IGRT (modern external beam), 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 LAURA, 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 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 (unresectable stage iii), which of the standard options do you recommend and why?
    Why: Guideline options include: Concurrent platinum chemoradiation followed by osimertinib until progression (LAURA) rather than durvalumab.
  8. Am I a candidate for Osimertinib, 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 LAURA 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

Brain and leptomeningeal metastases

2 options

Osimertinib has high brain penetration and is preferred; stereotactic radiosurgery for symptomatic or large lesions; high-dose osimertinib for leptomeningeal disease.

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.

A single very high dose, or a few doses, aimed at a small brain or spine target with millimetre precision, replacing whole-brain radiotherapy for most brain metastases.

  • One to five sessions
  • Spares healthy brain
  • Treats targets surgery cannot reach
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

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.

  • Limited to small targets
  • Radiation necrosis in a minority
  • Needs precise imaging and immobilisation
Questions to ask about this decision
  1. Between Osimertinib and Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS), 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. Which side effects of Osimertinib 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.
  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 (brain and leptomeningeal metastases), which of the standard options do you recommend and why?
    Why: Guideline options include: Osimertinib has high brain penetration and is preferred; stereotactic radiosurgery for symptomatic or large lesions; high-dose osimertinib for leptomeningeal disease.
  7. Am I a candidate for Osimertinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

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.