Latest Cancer TreatmentsDr. Mohammadreza Dabiri
Dr. Mohammadreza Dabiriفارسی
Treatment regimen

First-line regimens for recurrent or metastatic head and neck cancer: pembrolizumab and EXTREME

Pembrolizumab with or without chemotherapy, or platinum-fluorouracil-cetuximab

Updated: 28 October 20261 min read5 references

Summary for doctors

  • PD-L1 (CPS) testing before choosing [1].
  • CPS 1 or more: pembrolizumab alone or with chemotherapy [1].
  • EXTREME for patients for whom immunotherapy is not suitable [2].

Dose and schedule

Pembrolizumab + platinum + fluorouracil

Recurrent or metastatic head and neck cancer, first lineCycle length: Every 21 days

Recurrent or metastatic head and neck cancer, first line

DrugDoseRouteSchedule
Phase 1: 6 cycles
Pembrolizumab200 mgIVDay 1
Cisplatin 100 mg/m² or carboplatin AUC 5IVDay 1
Fluorouracil1000 mg/m² a dayContinuous infusionDays 1 to 4
Phase 2
Pembrolizumab200 mgIVEvery 21 days
Cycle length
Every 21 days
Duration
Pembrolizumab up to 35 cycles

As in KEYNOTE-048 [1].

Dose source: [4].

Evidence: KEYNOTE-048 (2019)

EXTREME

The same use; without immunotherapy

The same use; without immunotherapy

DrugDoseRouteSchedule
Phase 1: 6 cycles
Cisplatin 100 mg/m² or carboplatin AUC 5IVDay 1
Fluorouracil1000 mg/m² a dayContinuous infusionDays 1 to 4
Cetuximab400 mg/m² (first dose), then 250 mg/m²IVWeekly
Phase 2
Cetuximab250 mg/m²IVWeekly
Cycle length
Chemotherapy every 21 days; cetuximab weekly
Duration
Maintenance cetuximab until progression

As in EXTREME [2].

Dose source: [5].

Evidence: EXTREME (2008)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Premedication and supportive care

  • Cetuximab: antihistamine premedication; acneiform rash (preventive doxycycline and cream), magnesium.
  • DPYD: before the first fluoropyrimidine dose, consider testing for DPD deficiency (DPYD genotype); in carriers of one reduced-function allele the starting dose is reduced by about 50%, and these drugs are contraindicated in complete deficiency [3].

Monitoring and dose adjustment

  • Blood counts, creatinine and electrolytes before each cycle; TSH, glucose, liver enzymes and creatinine at baseline and every 6 weeks; immune-related toxicity as in the immunotherapy toxicity lesson.

Main evidence

Show detailsHide

KEYNOTE-048: with CPS 1 or more, pembrolizumab with chemotherapy increased median survival from 10.4 to 13.6 months compared with EXTREME [1]. EXTREME: adding cetuximab to platinum-fluorouracil increased median survival from 7.4 to 10.1 months [2].

Related cancer types

Head and neck cancers

Treatment regimens (physicians)

Cisplatin with radiotherapy in head and neck cancerTPF (induction) regimen in head and neck cancer

References

5 references
Show all references, 3 with a study cardClose the reference list

Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.

  1. 1
    Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 studyBurtness B, Harrington KJ, Greil R, et al · Lancet · 2019;394:1915-1928
    Study cardDOIPubMed Back to text: 1 2 3 4
  2. 2
    Platinum-based chemotherapy plus cetuximab in head and neck cancerVermorken JB, Mesia R, Rivera F, et al · N Engl J Med · 2008;359:1116-27
    Study cardDOIPubMed Back to text: 1 2 3
  3. 3
    Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 UpdateAmstutz U, Henricks LM, Offer SM, et al · Clin Pharmacol Ther · 2018;103:210-216
    Study cardDOIPubMed Back to text
  4. 4
    KEYTRUDA (PEMBROLIZUMAB) — Prescribing InformationMerck Sharp & Dohme LLC · FDA label · 2026
    Source Back to text
  5. 5
    ERBITUX (CETUXIMAB) — Prescribing InformationImclone LLC · FDA label · 2026
    Source Back to text

This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.

Printed from the website; the full and up-to-date version: https://drdabiri.com/en/regimens/extreme-keynote-048/

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