| Setting | Treatment |
|---|---|
| Early / resectable NSCLC NSCLC · no mets · operable | Surgery — lobectomy + mediastinal nodal sampling
the anchor of curative treatment Perioperative chemo-immunotherapy around surgery
neoadjuvant-only nivolumab (CheckMate-816) (5-yr update confirms an OS benefit, ~30% reduction in risk of death, ASCO 2025) · full perioperative (neo + adjuvant) pembrolizumab (KEYNOTE-671) or durvalumab (AEGEAN) EGFR-mutant → adjuvant osimertinib ×3 yr (ADAURA) ALK-positive → adjuvant alectinib (ALINA)
76% reduction in recurrence/death vs chemo · both targeted options REPLACE chemo-IO when the driver is present Medically inoperable → SABR
stereotactic ablative radiotherapy |
| Stage III, unresectable NSCLC · N2/N3 or unresectable · no mets | Concurrent chemoradiotherapy → consolidation durvalumab (PACIFIC) EGFR-mutant → consolidation osimertinib instead (LAURA)
PFS 39.1 vs 5.6 months ⚠ Durvalumab CONCURRENTLY with chemoRT does not help (PACIFIC-2)
it stays sequential / consolidative — after chemoRT finishes |
| Metastatic NSCLC — DRIVER-POSITIVE NGS: actionable driver found | Matched TKI — the driver picks the drug
⚠ NGS must be back before first-line treatment. Most of these are absent in any given patient — scan for the one you have: EGFR → osimertinib (FLAURA) (or amivantamab + lazertinib (MARIPOSA), 1st-line-approved 2024) · ALK → alectinib (ALEX) / lorlatinib (CROWN) · ROS1 → repotrectinib / crizotinib · BRAF V600E → dabrafenib + trametinib · MET exon-14 skipping → capmatinib / tepotinib · RET fusion → selpercatinib / pralsetinib · NTRK fusion → larotrectinib / entrectinib · HER2-mutant → trastuzumab deruxtecan (or zongertinib, an oral HER2 TKI, approved 2025) ⚠ KRAS-G12C is NOT a first-line driver
treat as driver-negative below (PD-L1-stratified chemo ± IO); sotorasib / adagrasib are reserved for 2nd-line+ ⚠ NOT immunotherapy first for any driver above |
| Metastatic NSCLC — DRIVER-NEGATIVE NGS: no actionable driver (includes KRAS-G12C) + PD-L1 TPS | PD-L1 ≥50% → pembrolizumab alone (KEYNOTE-024) PD-L1 <50% → chemo + pembrolizumab
(KEYNOTE-189) non-squamous · (KEYNOTE-407) squamous Chemo backbone
non-squamous → platinum + pemetrexed · squamous → platinum + gemcitabine / paclitaxel Palliative RT for symptomatic sites · brain mets → SRS / WBRT |
| SCLC — LIMITED stage confined to one hemithorax, fits one RT field | Platinum + etoposide + concurrent thoracic RT → consolidation durvalumab (ADRIATIC)
27% reduction in risk of death; median OS 55.9 vs 33.4 months — the first phase 3 survival gain in limited-stage SCLC in decades Consider PCI or MRI surveillance
prophylactic cranial irradiation |
| SCLC — EXTENSIVE stage distant metastases | Platinum + etoposide + a PD-L1 inhibitor
atezolizumab (IMpower133) or durvalumab (CASPIAN) 2nd line → TARLATAMAB is PREFERRED over chemotherapy (DeLLphi-304)
a DLL3 bispecific T-cell engager · phase 3 randomised it against chemo — and lurbinectedin, topotecan and amrubicin were the COMPARATOR arm: median OS 13.6 vs 8.3 mo, HR 0.60, 12-mo OS 53% vs 37% · ⚠ it was also BETTER TOLERATED (fewer grade ≥3 treatment-related AEs, fewer interruptions/reductions) — so the usual reason for holding it back does not hold · earlier accelerated approval on (DeLLphi-301) ⚠ Do NOT save tarlatamab for last
giving lurbinectedin / topotecan first and holding tarlatamab in reserve gives the patient the arm that LOST the trial, at the point they are fittest to tolerate the better drug. The legitimate reasons to use chemo instead are logistics or access, not efficacy: tarlatamab needs step-up dosing with CRS/ICANS monitoring capacity, and it must be available/funded Chemotherapy options if tarlatamab is unavailable → lurbinectedin · topotecan · amrubicin
and if PLATINUM-SENSITIVE relapse (beyond ~6 months) → platinum re-challenge is also legitimate — do not skip past it |