Metastatic NSCLC: No Targetable Driver, First-Line: the algorithm in words
Starting point: Metastatic NSCLC no targetable driver PD-L1 tested. Full background: NSCLC (Part 2): Stage IV, Targeted and Systemic Therapy notes.
- PD-L1 ≥ 50% (first-line): Low burden: Pembrolizumab monotherapy (KEYNOTE-024 / 042); High burden: Chemo + pembrolizumab (KEYNOTE-189).
- PD-L1 1-49% / nonsquamous (first-line): Combo: Carbo / pemetrexed + pembro (KEYNOTE-189).
- Squamous (first-line): Combo: Carbo / taxane + pembro (KEYNOTE-407).
- PD-L1 < 1% (first-line): Dual-IO: Nivo + ipi + 2 cycles chemo (CheckMate 9LA).
- Second-line (second-line): Antiangiogenic: Docetaxel + ramucirumab (REVEL); Cytotoxic: Docetaxel single agent (if ramucirumab unavailable).
- Third-line + (later-line): Cytotoxic: Single-agent chemo not used (pemetrexed / gemcitabine); Always: Clinical trial / supportive care (performance-status based).