Study aid only. Verify against current guidelines, primary literature, staging manuals, and prescribing information before clinical use.

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Recurrent / Metastatic HNSCC — Systemic Therapy

First-line Second-line SECOND-LINE Recurrent / metastatic HNSCC (squamous) 1L · PD-L1 CPS ≥ 1 1L · PD-L1 CPS < 1 Subsequent line Biomarker-selected Mono Pembrolizumab KEYNOTE-048 ↗ Combo Pembrolizumab + platinum / 5-FU KEYNOTE-048 ↗ Combo Pembrolizumab + platinum / 5-FU KEYNOTE-048 ↗ Alternative Platinum / 5-FU + cetuximab EXTREME ↗ IO Nivolumab CheckMate 141 ↗ Cytotoxic Docetaxel / methotrexate / cetuximab single agents ↗ CPS ≥ 20 Ipilimumab + nivolumab CheckMate 651 ↗ FGFR Erdafitinib FGFR mutation/fusion ↗ HER2 3+ Trastuzumab deruxtecan DESTINY-PanTumor02 ↗