The first 60 days: EGFR-mutated non-small-cell lung cancer
EGFR-mutated lung cancer is driven by a single faulty growth receptor and is treated first with a pill rather than chemotherapy. Osimertinib keeps the disease under control for about a year and a half on average, adding chemotherapy or the antibody amivantamab extends that further, and three years of osimertinib after surgery roughly halves the risk of death in early-stage disease. Below, week by week, is what OnCo's record of EGFR-mutated 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.
Weeks 1 to 2
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Biomarkers your report may list
EGFR mutation by tissue or plasma sequencing before first-line therapy (exon 19 deletion, L858R, exon 20 insertion, uncommon)T790M and C797S at progressionMET amplification at progression (fluorescence in situ hybridisation or sequencing)Circulating tumour DNA clearance during treatment (under study)Repeat biopsy at progression for small-cell transformationPD-L1 (of limited use; checkpoint inhibitors work poorly)
Ask which of these were tested and what the results were; see the report reader for what each value means.
Tests and imaging linked to this cancer
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.
- PathologistNamed in the standard of care for: Advanced, after osimertinib.
- SurgeonNamed in the standard of care for: Resected stage IB to IIIA.
- Medical oncologistNamed in the standard of care for: Advanced, first line (exon 19 deletion or L858R), Advanced, exon 20 insertion, Advanced, after osimertinib, Resected stage IB to IIIA and 2 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Unresectable stage III, Brain and leptomeningeal metastases.
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.
Concurrent platinum chemoradiation followed by osimertinib until progression (LAURA) rather than durvalumab.
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.
Amivantamab plus carboplatin-pemetrexed first line (PAPILLON); sunvozertinib after platinum chemotherapy.
AmivantamabA 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 InsertionsSunvozertinibAssessing an Oral EGFR Inhibitor, Sunvozertinib in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR or HER2 Mutation (WU-KONG1)EGFR exon 20 insertionCarboplatinPemetrexedBiopsy 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.
AmivantamabA 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 FailureSavolitinibOsimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior OsimertinibDatopotamab deruxtecanTROPION-Lung05MET amplification (bypass resistance)EGFR C797SHistologic transformationPlatinum + etoposide (EP / CE)Surgery, adjuvant platinum chemotherapy where indicated, then three years of osimertinib (ADAURA).
Osimertinib has high brain penetration and is preferred; stereotactic radiosurgery for symptomatic or large lesions; high-dose osimertinib for leptomeningeal disease.
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 EGFR mutation by tissue or plasma sequencing before first-line therapy, T790M and C797S at progression, MET amplification at progression, Circulating tumour DNA clearance during treatment, Repeat biopsy at progression for small-cell transformation), 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 EGFR exon 19 deletion adenocarcinoma, EGFR L858R adenocarcinoma, EGFR exon 20 insertion.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Advanced, first line (exon 19 deletion or L858R)
- For my situation (advanced, first line (exon 19 deletion or l858r)), which of the standard options do you recommend and 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.
- Am I a candidate for Osimertinib, Amivantamab, Lazertinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of FLAURA and FLAURA2 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Advanced, exon 20 insertion
- For my situation (advanced, exon 20 insertion), which of the standard options do you recommend and why?Guideline options include: Amivantamab plus carboplatin-pemetrexed first line (PAPILLON); sunvozertinib after platinum chemotherapy.
- Am I a candidate for Amivantamab, Sunvozertinib, Carboplatin 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 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?Trial populations differ from individual patients; ask how closely you match.
Advanced, after osimertinib
- For my situation (advanced, after osimertinib), which of the standard options do you recommend and 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.
- Am I a candidate for Amivantamab, Savolitinib, Datopotamab deruxtecan 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 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?Trial populations differ from individual patients; ask how closely you match.
Resected stage IB to IIIA
- For my situation (resected stage ib to iiia), which of the standard options do you recommend and why?Guideline options include: Surgery, adjuvant platinum chemotherapy where indicated, then three years of osimertinib (ADAURA).
- Am I a candidate for Osimertinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ADAURA apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Unresectable stage III
- For my situation (unresectable stage iii), which of the standard options do you recommend and why?Guideline options include: Concurrent platinum chemoradiation followed by osimertinib until progression (LAURA) rather than durvalumab.
- Am I a candidate for Osimertinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of LAURA apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Brain and leptomeningeal metastases
- For my situation (brain and leptomeningeal metastases), which of the standard options do you recommend and 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.
- Am I a candidate for Osimertinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Savolitinib, Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib, Patritumab deruxtecan, HERTHENA-Lung02?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 “No head-to-head trial compares the three first-line strategies, and the added toxicity of the combinations falls on every patient for a benefit concentrated in some”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Most resistance to osimertinib has no identifiable mechanism and no targeted option”. 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
- 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 InsertionsPhase 3 · active · NCT04538664A Randomized, Open-label Phase 3 Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Patients With EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
- REZILIENT3 (REsearching ZIpaLertinib In Egfr Non-small Cell Lung Cancer Tumors)Phase 3 · active · NCT05973773Randomized, Controlled, Open-label, Phase 3, Global Multi - Center Trial to Assess the Efficacy and Safety of Zipalertinib Plus Chemotherapy Versus Chemotherapy Alone, in Patients With Previously Untreated, Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer (NSCLC) With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) Mutations
- 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.
- Assessing an Oral EGFR Inhibitor, Sunvozertinib in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR or HER2 Mutation (WU-KONG1)Phase 1/2 · active · NCT03974022A Phase I/II, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of DZD9008 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) With EGFR or HER2 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.
- EGFR-mutated non-small-cell lung cancer: the full pageEGFR-mutated lung cancer is driven by a single faulty growth receptor and is treated first with a pill rather than chemotherapy. Osimertinib keeps the disease under control for about a year and a half on average, adding chemotherapy or the antibody amivantamab extends that further, and three years of osimertinib after surgery roughly halves the risk of death in early-stage disease.
- 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.
Words this page and the cancer page use
- EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M): Lung cancers with a mutated EGFR gene are treated with EGFR pills, but which pill and how well it works depends on exactly where the mutation is.
- EGFR C797S: A mutation that stops osimertinib from binding to EGFR; the main on-target way lung cancers escape it.
- EGFR exon 20 insertion: A rarer EGFR mutation (~2% of lung cancers) that does not respond to standard EGFR pills and needs its own drugs.
- MET amplification (bypass resistance): When lung cancer switches on the MET receptor to bypass a blocked EGFR pill.
- EGFR exon 19 deletion & L858R: Exon 19 deletion and L858R are the two common EGFR mutations, together ~85% of EGFR-mutant lung cancer, and both respond to EGFR pills.
- Leptomeningeal disease: Cancer cells spreading in the fluid and membranes that bathe the brain and spinal cord, rather than as a solid lump.
- Lobectomy: Removing one lobe of the lung (the right lung has three, the left two).
- Driver mutation: One of the few mutations in a tumour that actually causes it to grow.
- Oncogene addiction: When a cancer depends so completely on one mutated gene that blocking it collapses the tumour.
- 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.
Every term links to the glossary.