The first 60 days: Non-small-cell lung cancer
Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story. Below, week by week, is what OnCo's record of 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.
- CT and PET-CT, brain MRI, biopsy with PD-L1 and a molecular panel (EGFR, ALK, ROS1, KRAS and others), mediastinal staging, lung function tests.
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.
- PathologistNamed in the standard of care for: Screening (age 50-80, ≥20 pack-years), Metastatic, EGFR exon 19 del / L858R.
- RadiologistNamed in the standard of care for: Screening, Screening (age 50-80, ≥20 pack-years).
- SurgeonNamed in the standard of care for: Early stage, Screening (age 50-80, ≥20 pack-years), Stage I-II resectable.
- Medical oncologistNamed in the standard of care for: Early stage, Stage III unresectable, Metastatic, driver-positive, Metastatic, driver-negative and 14 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Early stage, Stage III unresectable, Stage I-II resectable.
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.
Annual low-dose CT for high-risk smokers (NLST, NELSON); AI nodule scoring emerging.
Annual low-dose CT with Lung-RADS reporting; AI nodule scoring emerging; robotic bronchoscopy for peripheral nodule biopsy.
Surgery or SBRT; perioperative chemo-immunotherapy; adjuvant osimertinib (EGFR) or alectinib (ALK).
Lobectomy or segmentectomy (small peripheral) with nodal staging; SBRT if inoperable. Stage IB-IIIA: neoadjuvant chemo-IO (CheckMate 816) or perioperative chemo-IO (KEYNOTE-671); adjuvant osimertinib if EGFR-mutant (ADAURA), alectinib if ALK-positive (ALINA); adjuvant chemotherapy otherwise for stage II+.
Chemoradiation → durvalumab (PACIFIC) or osimertinib (LAURA, EGFR).
Concurrent platinum chemoradiation → durvalumab 1 year (PACIFIC), or osimertinib until progression if EGFR-mutant (LAURA). Proton therapy in selected cases.
- 7.Metastatic, driver-positiveESMO-MCBS 3 (DESTINY-Lung02, HER2-mutant, second line), NCCN Guidelines: Non-Small Cell Lung Cancer
Matched TKI or bispecific; ADCs after progression.
PD-(L)1 ± chemotherapy; docetaxel or ADC/TTFields second line.
First line: osimertinib ± platinum-pemetrexed (FLAURA2) or amivantamab + lazertinib (MARIPOSA, OS benefit). Progression: re-biopsy/ctDNA; amivantamab + chemotherapy (MARIPOSA-2), Dato-DXd (TROPION-Lung05), platinum doublet; MET TKI add-on if MET-amplified; platinum-etoposide if small-cell transformation.
Amivantamab + platinum-pemetrexed (PAPILLON); sunvozertinib later line.
Lorlatinib (CROWN; 5-year PFS 60%) or alectinib first line; on progression, neladalkib (under review) or lorlatinib if not used; local therapy for oligoprogression; chemotherapy.
Repotrectinib or zidesamtinib (2026) first line; entrectinib/crizotinib alternatives.
First line: PD-(L)1 ± chemotherapy by PD-L1 (G12C inhibitor + IO combinations in phase 3: olomorasib SUNRAY-01, divarasib Krascendo 2). Second line: sotorasib or adagrasib (CodeBreaK 200, KRYSTAL-12); divarasib superior head-to-head (Krascendo 1, 2026).
Dabrafenib + trametinib or encorafenib + binimetinib first line; chemo-IO as alternative.
Capmatinib or tepotinib first line; telisotuzumab vedotin for c-Met-overexpressing EGFR-wild-type disease after chemotherapy (accelerated 2025).
Selpercatinib first line (LIBRETTO-431); pralsetinib alternative.
First line: zongertinib (2026) or chemo-IO; sevabertinib (Nov 2025) or T-DXd after prior therapy.
Larotrectinib, entrectinib, or repotrectinib (tumour-agnostic).
Pembrolizumab (KEYNOTE-024) or cemiplimab monotherapy; add chemotherapy for high burden or rapid progression. Ivonescimab beat pembrolizumab in China (HARMONi-2); not approved in the US.
Pembrolizumab + platinum doublet (KEYNOTE-189 non-squamous; KEYNOTE-407 squamous); nivolumab + ipilimumab ± chemotherapy; tremelimumab + durvalumab + chemotherapy for PD-L1-negative or STK11/KEAP1-altered disease. Second line: docetaxel ± ramucirumab, TTFields, or trials of ADCs.
Pembrolizumab + carboplatin + (nab-)paclitaxel (KEYNOTE-407); no ADC approved (TROPION-Lung01 showed no benefit in squamous); ivonescimab + chemotherapy under study (HARMONi-3).
- Is there an EGFR mutation or ALK fusion?
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, ALK, ROS1, BRAF V600E, MET ex14 / amplification / c-MET IHC), 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 Adenocarcinoma, Squamous, EGFR-mutant.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Screening
- For my situation (screening), which of the standard options do you recommend and why?Guideline options include: Annual low-dose CT for high-risk smokers (NLST, NELSON); AI nodule scoring emerging.
Early stage
- For my situation (early stage), which of the standard options do you recommend and why?Guideline options include: Surgery or SBRT; perioperative chemo-immunotherapy; adjuvant osimertinib (EGFR) or alectinib (ALK).
- 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.
Stage III unresectable
- For my situation (stage iii unresectable), which of the standard options do you recommend and why?Guideline options include: Chemoradiation → durvalumab (PACIFIC) or osimertinib (LAURA, EGFR).
- Am I a candidate for Durvalumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- For my situation (stage iii unresectable), which of the standard options do you recommend and why?Guideline options include: Concurrent platinum chemoradiation → durvalumab 1 year (PACIFIC), or osimertinib until progression if EGFR-mutant (LAURA). Proton therapy in selected cases.
- Am I a candidate for Durvalumab, 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 PACIFIC and LAURA apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, driver-positive
- For my situation (metastatic, driver-positive), which of the standard options do you recommend and why?Guideline options include: Matched TKI or bispecific; ADCs after progression.
- Am I a candidate for Osimertinib, Amivantamab, Lorlatinib or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic, driver-negative
- For my situation (metastatic, driver-negative), which of the standard options do you recommend and why?Guideline options include: PD-(L)1 ± chemotherapy; docetaxel or ADC/TTFields second line.
- Am I a candidate for Pembrolizumab, Nivolumab, Optune / Optune Pax (TTFields), and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Screening (age 50-80, ≥20 pack-years)
- For my situation (screening (age 50-80, ≥20 pack-years)), which of the standard options do you recommend and why?Guideline options include: Annual low-dose CT with Lung-RADS reporting; AI nodule scoring emerging; robotic bronchoscopy for peripheral nodule biopsy.
- How do the results of NLST & NELSON (low-dose CT screening) apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Stage I-II resectable
- For my situation (stage i-ii resectable), which of the standard options do you recommend and why?Guideline options include: Lobectomy or segmentectomy (small peripheral) with nodal staging; SBRT if inoperable. Stage IB-IIIA: neoadjuvant chemo-IO (CheckMate 816) or perioperative chemo-IO (KEYNOTE-671); adjuvant osimertinib if EGFR-mutant (ADAURA), alectinib if ALK-positive (ALINA); adjuvant chemotherapy otherwise for stage II+.
- Am I a candidate for Osimertinib, Alectinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CheckMate 816 and KEYNOTE-671 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, EGFR exon 19 del / L858R
- For my situation (metastatic, egfr exon 19 del / l858r), which of the standard options do you recommend and why?Guideline options include: First line: osimertinib ± platinum-pemetrexed (FLAURA2) or amivantamab + lazertinib (MARIPOSA, OS benefit). Progression: re-biopsy/ctDNA; amivantamab + chemotherapy (MARIPOSA-2), Dato-DXd (TROPION-Lung05), platinum doublet; MET TKI add-on if MET-amplified; platinum-etoposide if small-cell transformation.
- Am I a candidate for Osimertinib, Amivantamab, Lazertinib 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 FLAURA2 and MARIPOSA apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, EGFR exon 20 insertion
- For my situation (metastatic, egfr exon 20 insertion), which of the standard options do you recommend and why?Guideline options include: Amivantamab + platinum-pemetrexed (PAPILLON); sunvozertinib later line.
- Am I a candidate for Amivantamab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic, ALK-rearranged
- For my situation (metastatic, alk-rearranged), which of the standard options do you recommend and why?Guideline options include: Lorlatinib (CROWN; 5-year PFS 60%) or alectinib first line; on progression, neladalkib (under review) or lorlatinib if not used; local therapy for oligoprogression; chemotherapy.
- Am I a candidate for Lorlatinib, Alectinib, Neladalkib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CROWN and ALKOVE-1 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, ROS1-rearranged
- For my situation (metastatic, ros1-rearranged), which of the standard options do you recommend and why?Guideline options include: Repotrectinib or zidesamtinib (2026) first line; entrectinib/crizotinib alternatives.
- Am I a candidate for Repotrectinib, Zidesamtinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic, KRAS G12C
- For my situation (metastatic, kras g12c), which of the standard options do you recommend and why?Guideline options include: First line: PD-(L)1 ± chemotherapy by PD-L1 (G12C inhibitor + IO combinations in phase 3: olomorasib SUNRAY-01, divarasib Krascendo 2). Second line: sotorasib or adagrasib (CodeBreaK 200, KRYSTAL-12); divarasib superior head-to-head (Krascendo 1, 2026).
- Am I a candidate for Sotorasib, Adagrasib, Divarasib 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.
Metastatic, BRAF V600E
- For my situation (metastatic, braf v600e), which of the standard options do you recommend and why?Guideline options include: Dabrafenib + trametinib or encorafenib + binimetinib first line; chemo-IO as alternative.
- Am I a candidate for Dabrafenib + trametinib, Encorafenib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic, MET exon 14 skipping
- For my situation (metastatic, met exon 14 skipping), which of the standard options do you recommend and why?Guideline options include: Capmatinib or tepotinib first line; telisotuzumab vedotin for c-Met-overexpressing EGFR-wild-type disease after chemotherapy (accelerated 2025).
- Am I a candidate for Capmatinib & tepotinib, Telisotuzumab vedotin, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of TeliMET NSCLC-01 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, RET-fusion
- For my situation (metastatic, ret-fusion), which of the standard options do you recommend and why?Guideline options include: Selpercatinib first line (LIBRETTO-431); pralsetinib alternative.
- Am I a candidate for Selpercatinib, Pralsetinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of LIBRETTO-431 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, HER2-mutant
- For my situation (metastatic, her2-mutant), which of the standard options do you recommend and why?Guideline options include: First line: zongertinib (2026) or chemo-IO; sevabertinib (Nov 2025) or T-DXd after prior therapy.
- Am I a candidate for Zongertinib, Sevabertinib, Trastuzumab deruxtecan, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of SOHO-01 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, NTRK-fusion
- For my situation (metastatic, ntrk-fusion), which of the standard options do you recommend and why?Guideline options include: Larotrectinib, entrectinib, or repotrectinib (tumour-agnostic).
- Am I a candidate for Repotrectinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic, driver-negative, PD-L1 TPS ≥50%
- For my situation (metastatic, driver-negative, pd-l1 tps ≥50%), which of the standard options do you recommend and why?Guideline options include: Pembrolizumab (KEYNOTE-024) or cemiplimab monotherapy; add chemotherapy for high burden or rapid progression. Ivonescimab beat pembrolizumab in China (HARMONi-2); not approved in the US.
- Am I a candidate for Pembrolizumab, Cemiplimab, Ivonescimab, 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 and HARMONi-2 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, driver-negative, PD-L1 TPS <50%
- For my situation (metastatic, driver-negative, pd-l1 tps <50%), which of the standard options do you recommend and why?Guideline options include: Pembrolizumab + platinum doublet (KEYNOTE-189 non-squamous; KEYNOTE-407 squamous); nivolumab + ipilimumab ± chemotherapy; tremelimumab + durvalumab + chemotherapy for PD-L1-negative or STK11/KEAP1-altered disease. Second line: docetaxel ± ramucirumab, TTFields, or trials of ADCs.
- Am I a candidate for Pembrolizumab, Nivolumab, Ipilimumab or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic, squamous
- For my situation (metastatic, squamous), which of the standard options do you recommend and why?Guideline options include: Pembrolizumab + carboplatin + (nab-)paclitaxel (KEYNOTE-407); no ADC approved (TROPION-Lung01 showed no benefit in squamous); ivonescimab + chemotherapy under study (HARMONi-3).
- Am I a candidate for Pembrolizumab, Paclitaxel / nab-paclitaxel, Carboplatin, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of TROPION-Lung01 and HARMONi-3 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 Ivonescimab, Izalontamab brengitecan, Sacituzumab tirumotecan, Tilatamig samrotecan?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 “Resistance to every TKI”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Squamous histology has few targets”. 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 Clinical Study of JMT101 in Combination With Osimertinib Versus Osimertinib Alone as First-Line Treatment for Patients With Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) Sensitive MutationsPhase 3 · recruiting · NCT06735391A Phase 3 Clinical Study of JMT101 in Combination With Osimertinib Versus Osimertinib Alone as First-Line Treatment for Patients With Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) Sensitive Mutations
- A Clinical Study of Pembrolizumab (+) Berahyaluronidase Alfa (MK-3475A) to Treat Newly-diagnosed Metastatic Non-small Cell Lung Cancer (MK-3475A-F84)Phase 3 · active · NCT06698042A Phase 3 Randomized, Open-label Clinical Study to Evaluate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Versus Intravenous Pembrolizumab, in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer With PD-L1 TPS 50% or Greater
- A Clinical Trial of Adjuvant Intismeran (V940) With or Without Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) in High-Risk Stage I Phase 3 · recruiting · NCT07513376A Phase 3, Randomized, Placebo-Controlled Study of Adjuvant Intismeran Autogene Plus Subcutaneous Pembrolizumab and Berahyaluronidase Alfa (MK-3475A) or Intismeran Autogene Monotherapy Versus Placebo in Participants With Completely Resected High-Risk Stage I Non-Small Cell Lung Cancer (INTerpath-014)
- A Clinical Trial of Calderasib (MK-1084) and Durvalumab in People With Non-Small Cell Lung Cancer (MK-1084-015/KANDLELIT-015)Phase 3 · recruiting · NCT07554339A Phase 3, Randomized, Double-blind, Placebo- and Active-Comparator-Controlled Study of MK-1084 Plus Durvalumab Versus Placebo Plus Durvalumab in Participants With Locally Advanced, Unresected KRAS G12C-Mutant Non-Small Cell Lung Cancer Without Disease Progression Following Definitive Platinum-Based Chemoradiotherapy (KANDLELIT-015)
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Non-small-cell lung cancer: the full pageNon-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment journey: Stage II-IIIA (resectable)Molecular testing splits the road: without a driver mutation, chemo-immunotherapy comes before surgery and immunotherapy after; with an EGFR or ALK alteration, surgery is followed by a targeted tablet for two to three years.
- Guidelines comparedNCCN, ESMO and NICE side by side for this cancer.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Histology: The study of tissue under the microscope.
- 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.
- Tumour proportion score (TPS): The PD-L1 score used in lung cancer: the percentage of tumour cells that stain positive.
- 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.
- MET amplification (bypass resistance): When lung cancer switches on the MET receptor to bypass a blocked EGFR pill.
- EGFR C797S: A mutation that stops osimertinib from binding to EGFR; the main on-target way lung cancers escape it.
- Lobectomy: Removing one lobe of the lung (the right lung has three, the left two).
- 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.
- Oligoprogression: When only one or two spots grow on an otherwise working targeted therapy; treat the spots and keep the pill.
- STK11 / KEAP1 co-mutations: Two genes whose loss, often alongside a KRAS mutation, makes lung cancer 'cold' to immunotherapy and shortens survival on standard treatment.
Every term links to the glossary.