Pembrolizumab with metformin: 50% response in a small phase 2 head and neck cancer trial

Design

Phase 2 randomised feasibility trial of two sequences, no control arm

Population

21 patients with recurrent or metastatic HNSCC (18 evaluable)

Primary outcome

Overall response rate (RECIST 1.1)

Effect

ORR 50% (95% CI 29% to 71%); 4 complete, 5 partial responses

This phase 2 feasibility trial, published 15 September in Clinical Cancer Research, randomised 21 patients with recurrent or metastatic head and neck squamous cell carcinoma to two sequences of metformin extended-release (up to 2,000 mg daily) combined with pembrolizumab 200 mg every three weeks.

Of 18 evaluable patients, four had complete and five partial responses — an overall response rate of 50% (95% CI 29% to 71%). Ten patients had oropharyngeal tumours, nine of them p16-positive. Five grade 3 adverse events occurred, all gastrointestinal or constitutional. Metformin increased peripheral natural killer cell maturation and cytotoxicity.

Pembrolizumab alone produces responses in fewer than one in five of these patients, so a 50% figure is striking. But with 18 patients, a high proportion of HPV-related tumours and no control arm, it is a signal for a randomised trial, not a reason to add metformin now.

• The combination of metformin and pembrolizumab was tolerable, with mainly gastrointestinal side effects.
• The response rate was 50% in 18 evaluable patients, many with HPV-related oropharyngeal cancer.
• Do not add metformin to immunotherapy outside a trial on this evidence.
• Watch for a randomised trial before changing practice.

Why it matters

Points to a cheap, familiar drug as a possible immunotherapy partner in a disease with few options.

Don't overread it

Phase 2, 18 evaluable patients, no pembrolizumab-alone control, and many p16-positive tumours that respond better anyway.

The statistics, in plain English

The 95% confidence interval of 29% to 71% is wide because only 18 patients were assessed; the true response rate could be much lower.

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