EvidenceRecurrent or metastatic head and neck squamous cell carcinoma

For the majority of the world's head and neck cancer patients who cannot afford full-dose checkpoint inhibitors, a low dose added to oral metronomic chemotherapy is a tested alternative that improves survival. It also challenges the assumption that approved doses are the necessary doses: pharmacology had long suggested receptor saturation at far lower exposures.

TPEx is a less toxic, more convenient chemotherapy backbone for patients who need cetuximab-based first-line therapy, for instance when immunotherapy is unsuitable.

Patients with head and neck squamous cell cancer that has recurred or spread should be treated first with pembrolizumab: alone if their tumour is strongly PD-L1 positive and they can wait for a slower response, or with chemotherapy if the tumour is bulky or PD-L1 low. Cetuximab-based chemotherapy is no longer the default. Long-term follow-up shows a small but real group of patients alive at four to five years, which was almost unheard of before.

PD-1 blockade after platinum became standard, and the trial opened the way for first-line pembrolizumab in KEYNOTE-048.

EXTREME was the first-line standard for a decade and remains the option for patients unsuitable for pembrolizumab; it was the comparator that KEYNOTE-048 improved upon.