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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
When head and neck cancer comes back where it cannot be removed, or spreads elsewhere, it is treated to extend life rather than cure: pembrolizumab, alone or with chemotherapy, is the first choice, cetuximab-based regimens and cheap oral chemotherapy are alternatives, and antibodies that hit two targets at once are in late-stage trials.
Recurrent or metastatic head and neck squamous cell carcinoma covers disease that returns in the head and neck after radiotherapy or surgery and cannot be salvaged, and disease that has spread to the lungs, bone or liver. A minority with locoregional recurrence are cured by salvage surgery or re-irradiation, and a few with a single metastasis are treated with stereotactic radiotherapy; for the rest treatment is systemic and palliative. Work-up includes biopsy, PD-L1 combined positive score, HPV status of oropharyngeal primaries and the interval since platinum, since progression within six months of platinum defines platinum-refractory disease.
First-line treatment was defined for a decade by EXTREME (2008), in which cetuximab with platinum and fluorouracil gave median overall survival of 10.1 against 7.4 months. CheckMate 141 (2016) then showed that nivolumab extended survival after platinum failure (7.5 against 5.1 months), and KEYNOTE-048 (2019) moved immunotherapy to the front: pembrolizumab alone gave median survival of 14.9 against 10.7 months in tumours with a combined positive score of 20 or more, and pembrolizumab with chemotherapy gave 13.0 against 10.7 months in the whole population, with a durable tail at five years. Pembrolizumab-based treatment is now the standard, EXTREME or its docetaxel variant TPExtreme the option for rapidly progressing disease or after immunotherapy, and cetuximab sarotalocan photoimmunotherapy is approved in Japan for locoregional recurrence.
| Setting | Approach | Guideline |
|---|---|---|
| First line, combined positive score 1 or more | Pembrolizumab alone for indolent disease, especially with a score of 20 or more; pembrolizumab with platinum and fluorouracil for bulky or symptomatic disease (KEYNOTE-048). | NCCN Category 1 |
| First line, combined positive score under 1 or immunotherapy unsuitable | Pembrolizumab with platinum-fluorouracil, or cetuximab with platinum-fluorouracil (EXTREME) or with docetaxel and platinum (TPExtreme). | NCCN Category 1 |
| After platinum and immunotherapy | Cetuximab, docetaxel, paclitaxel or methotrexate as single agents; nivolumab or pembrolizumab if not given before (CheckMate 141); clinical trials. | NCCN Category 1 (nivolumab, pembrolizumab) |
| Locoregional recurrence | Salvage surgery where resectable; re-irradiation with intensity-modulated or stereotactic techniques in selected patients; cetuximab sarotalocan photoimmunotherapy in Japan. | ESMO-MCBS 2 (cetuximab sarotalocan, single-arm) |
| Resource-limited settings | Oral metronomic methotrexate with celecoxib; low-dose nivolumab added where affordable; metronomic tablets with paclitaxel-carboplatin (METRO PLUS). | not mapped |
| Symptom control | Palliative radiotherapy for bleeding, pain or airway compromise; early involvement of palliative care, nutrition and speech and swallowing teams. | not mapped |