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16 standard-of-care settings across 4 lines and 12 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.
| Line | All comers | ALK | BRAF | EGFR | EGFR exon 20 | HER2 | KRAS G12C | MET | NTRK | PD-L1 | RET | ROS1 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Screening, prevention and diagnosis | 1 | · | · | · | · | · | · | · | · | · | · | · |
| Early / localised | 1 | · | · | · | · | · | · | · | · | · | · | · |
| Locally advanced | 1 | · | · | · | · | · | · | · | · | · | · | · |
| Advanced, first line | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 2 | 1 | 1 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Screening (age 50-80, ≥20 pack-years) | Annual low-dose CT with Lung-RADS reporting; AI nodule scoring emerging; robotic bronchoscopy for peripheral nodule biopsy. | 83 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Stage I-II resectable | 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+. | 95 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Stage III unresectable | Concurrent platinum chemoradiation → durvalumab 1 year (PACIFIC), or osimertinib until progression if EGFR-mutant (LAURA). Proton therapy in selected cases. | 98 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Metastatic, squamous | Pembrolizumab + carboplatin + (nab-)paclitaxel (KEYNOTE-407); no ADC approved (TROPION-Lung01 showed no benefit in squamous); ivonescimab + chemotherapy under study (HARMONi-3). | 98 | ||
| ALK | Metastatic, ALK-rearranged | 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. | 90 | ||
| BRAF | Metastatic, BRAF V600E | Dabrafenib + trametinib or encorafenib + binimetinib first line; chemo-IO as alternative. | 97 | ||
| EGFR | Metastatic, EGFR exon 19 del / L858R | 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. | 95 | ||
| EGFR exon 20 | Metastatic, EGFR exon 20 insertion | Amivantamab + platinum-pemetrexed (PAPILLON); sunvozertinib later line. | 91 | ||
| HER2 | Metastatic, HER2-mutant | First line: zongertinib (2026) or chemo-IO; sevabertinib (Nov 2025) or T-DXd after prior therapy. | 97 | ||
| KRAS G12C | Metastatic, KRAS G12C | 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). | 96 | ||
| MET | Metastatic, MET exon 14 skipping | Capmatinib or tepotinib first line; telisotuzumab vedotin for c-Met-overexpressing EGFR-wild-type disease after chemotherapy (accelerated 2025). | 73 | ||
| NTRK | Metastatic, NTRK-fusion | Larotrectinib, entrectinib, or repotrectinib (tumour-agnostic). | 70 | ||
| PD-L1 | Metastatic, driver-negative, PD-L1 TPS ≥50% | 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. | 98 | ||
| PD-L1 | Metastatic, driver-negative, PD-L1 TPS <50% | 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. | 98 | ||
| RET | Metastatic, RET-fusion | Selpercatinib first line (LIBRETTO-431); pralsetinib alternative. | 94 | ||
| ROS1 | Metastatic, ROS1-rearranged | Repotrectinib or zidesamtinib (2026) first line; entrectinib/crizotinib alternatives. | 70 |
After the lung cancer pill stops working, an ADC that does not care which resistance mutation emerged.
If a lung cancer has a targetable mutation, give the pill first; immunotherapy works poorly in these tumours and raises the risk of severe side effects when a pill follows.
Enhertu and its DXd cousins can inflame the lungs; combining them with immunotherapy, radiation, or mTOR inhibitors stacks that risk.
Protons stop inside the tumour; modern X-ray beams (IMRT) still exit through healthy tissue. That physical difference only matters if it changes cure or late harm enough to justify the cost, which randomised adult trials have not settled.
Adding a TIGIT blocker to PD-1/PD-L1 blockade looked good in phase 2 and then failed repeatedly in phase 3.
Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.