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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.
The frontier is combinations that lift response rates above the roughly one in five seen with pembrolizumab alone. Petosemtamab, a bispecific antibody against EGFR and LGR5, produced responses in about six in ten untreated patients with pembrolizumab in phase 2 and is in the phase 3 LiGeR-HN1 and LiGeR-HN2 trials; ficerafusp alfa, which blocks EGFR and traps TGF-beta, is in FORTIFI-HN01 for HPV-negative disease; HB-200, an arenavirus-based vaccine against HPV16 E6 and E7, has been tested with pembrolizumab in HPV16-positive disease; and the EGFR antibody-drug conjugate MRG003 is in phase 3 against cetuximab or methotrexate. In India, Tata Memorial trials showed that oral methotrexate with celecoxib beat intravenous cisplatin (median survival 7.5 against 6.1 months), that adding one-twentieth of the usual nivolumab dose raised one-year survival from 16.3 to 43.4 percent, and, in METRO PLUS, that adding metronomic tablets to paclitaxel-carboplatin doubled median survival from 5 to 10 months.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
Site decides cause and behaviour: HPV drives oropharyngeal cancer, EBV drives nasopharyngeal cancer, tobacco drives oral and laryngeal cancer; all drain into the neck node levels that surgeons and radiotherapists map.
Same organ: Acinic cell carcinoma of the salivary glands, Carcinoma ex pleomorphic adenoma, Multiple endocrine neoplasia type 1 (MEN1), Multiple endocrine neoplasia type 2 (MEN2A and MEN2B), Hyperparathyroidism-jaw tumour syndrome (CDC73-related parathyroid carcinoma), Oropharyngeal cancer (tonsil and base of tongue), Laryngeal and hypopharyngeal cancer, Oral cavity cancer (mouth and tongue), Head and neck squamous cell carcinoma, Nasopharyngeal carcinoma, Salivary gland cancers, Papillary thyroid cancer, Follicular thyroid cancer, Medullary thyroid cancer, Anaplastic thyroid cancer, Thyroid cancer, Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma), NUT carcinoma (midline carcinoma with NUTM1 rearrangement), Parathyroid carcinoma, Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4), HPV-positive oropharyngeal cancer, HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer), Hypopharyngeal cancer, Adenoid cystic carcinoma, Salivary duct carcinoma, Mucoepidermoid carcinoma, Oral tongue and floor of mouth cancer, Buccal mucosa and gingivobuccal cancer (oral cancer in India), Lip cancer, Locoregionally advanced nasopharyngeal carcinoma (stage III to IVA), Recurrent and metastatic nasopharyngeal carcinoma, Esthesioneuroblastoma (olfactory neuroblastoma), Sinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma
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).
Pembrolizumab with platinum-fluorouracil, or cetuximab with platinum-fluorouracil (EXTREME) or with docetaxel and platinum (TPExtreme).
Cetuximab, docetaxel, paclitaxel or methotrexate as single agents; nivolumab or pembrolizumab if not given before (CheckMate 141); clinical trials.
Salvage surgery where resectable; re-irradiation with intensity-modulated or stereotactic techniques in selected patients; cetuximab sarotalocan photoimmunotherapy in Japan.
Oral metronomic methotrexate with celecoxib; low-dose nivolumab added where affordable; metronomic tablets with paclitaxel-carboplatin (METRO PLUS).
Palliative radiotherapy for bleeding, pain or airway compromise; early involvement of palliative care, nutrition and speech and swallowing teams.
Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Capecitabine: take within 30 minutes after a meal. DPD deficiency (DPYD variants) causes severe toxicity: pre-treatment genotyping is recommended in Europe.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Dose by Calvert formula using GFR (see the calculators).
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
See all on the product pages:CarboplatinCisplatinDocetaxelFluorouracil (5-FU)MethotrexateNivolumabPaclitaxel / nab-paclitaxelPembrolizumab·Printable cards in the navigator
Newly diagnosed? Read the first 60 days with Recurrent or metastatic head and neck squamous cell carcinoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked.