ADMEC-O (adjuvant nivolumab in completely resected Merkel cell carcinoma)

Merkel cell carcinoma relapses often after complete resection and radiotherapy, and until this trial there was no systemic standard for the situation. Twenty academic centres in Germany and the Netherlands randomised 179 patients 2 to 1 to nivolumab 480 mg every four weeks for a year or to observation. Sixty-five per cent had stage 3 or 4 disease, 68 per cent were 65 or older, and adjuvant radiotherapy was more common in the control group, which is an imbalance worth holding in mind.

At a median follow-up of 24.3 months, median disease-free survival had not been reached in either arm. Disease-free survival was 85 per cent at 12 months and 84 per cent at 24 months with nivolumab, against 77 and 73 per cent with observation, a hazard ratio of 0.58 (95 per cent confidence interval 0.30 to 1.12) whose interval crosses one. The authors state the effect as an absolute risk reduction of 9 percentage points at one year and 10 at two.

Safety is the other half of the trade: grade 3 or 4 adverse events in 48 of 115 treated patients (42 per cent) against 7 of 61 (11 per cent) under observation, with no treatment-related deaths.

The trial's own interpretation is unusually candid and should be quoted rather than smoothed: overall survival had ten events in the treatment group and six in the observation group, which is half the size, and is not mature enough to draw conclusions from. An accompanying comment in the same issue of the journal asked directly whether adjuvant nivolumab should be used on this evidence. It is a phase 2 result in a rare disease, which is often all a rare disease gets, and the honest description is a promising signal rather than a proven standard.