Pembrolizumab with metformin gave a 50% response rate in a small metastatic head and neck cancer study

Design

Phase II feasibility study, randomised to drug sequence only

Population

21 patients with recurrent or metastatic head and neck squamous cell carcinoma

Primary outcome

Overall response rate (RECIST 1.1)

Effect

ORR 50% (95% CI 29–71%) in 18 evaluable; 5 grade 3 adverse events

This phase II feasibility study enrolled 21 patients with recurrent or metastatic head and neck squamous cell carcinoma and randomised them only to the order of starting: metformin extended-release escalated to 2,000 mg before adding pembrolizumab 200 mg three-weekly, or pembrolizumab first. Ten had oropharyngeal cancer, nine of them p16-positive.

Of 18 patients evaluable, four had complete and five partial responses, a response rate of 50% (95% CI 29–71%). Five grade 3 adverse events occurred — nausea, diarrhoea, fatigue and weight loss — with no unexpected toxicity. Metformin increased the maturation and cytotoxic activity of circulating natural killer cells.

The response rate is well above what pembrolizumab usually achieves in this setting, and metformin is cheap and familiar, which makes the idea attractive in Indian oncology. But 18 patients with a high proportion of p16-positive oropharyngeal tumours cannot establish benefit, and there was no pembrolizumab-alone control.

• Do not add metformin to immunotherapy outside a trial on this evidence
• Continue metformin in patients with diabetes starting immunotherapy, as usual
• Record p16 status, which strongly influences immunotherapy response
• Look for randomised trials of the combination for eligible patients

Why it matters

A cheap, well-known drug may amplify immunotherapy, which would matter most where immunotherapy access is limited.

Don't overread it

A single-arm efficacy result from 18 patients — randomisation was only to drug sequence, so there is no comparison with pembrolizumab alone.

The statistics, in plain English

A 50% response rate from 18 patients has a confidence interval of 29–71%, so the true rate could be close to what immunotherapy alone achieves in favourable patients. Nearly half had p16-positive oropharyngeal cancer, which tends to respond better, and without a control arm the metformin contribution cannot be separated.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.