TUMORAPA (switching from a calcineurin inhibitor to sirolimus after a transplant skin cancer)

The immunosuppression that keeps a transplanted organ alive is what lets keratinocyte cancers grow, and a transplant recipient who has had one cutaneous squamous cell carcinoma will usually go on to have several. TUMORAPA tested the obvious intervention: change the immunosuppressive drug rather than treat the cancers one at a time. One hundred and twenty kidney transplant recipients on calcineurin inhibitors who had already had at least one cutaneous squamous cell carcinoma were randomised to switch to sirolimus, a mammalian target of rapamycin inhibitor with antitumour activity, or to carry on as they were.

Survival free of cutaneous squamous cell carcinoma was significantly longer in the sirolimus group. New squamous cell carcinomas developed in 14 of 64 patients (22 per cent) on sirolimus, six of them after the drug had been withdrawn, against 22 of 56 (39 per cent) on calcineurin inhibitors, with a median time to onset of 15 against 7 months (p=0.02) and a relative risk of 0.56 (95 per cent confidence interval 0.32 to 0.98). Graft function stayed stable in both groups.

The cost is the reason this is not done automatically. There were 60 serious adverse events in the sirolimus group against 14 in the calcineurin inhibitor group, an average of 0.938 against 0.250 per patient, and 23 per cent of the sirolimus group stopped the drug because of adverse events. Twice as many serious events occurred in patients switched rapidly as in those switched gradually, which is a practical instruction rather than a statistic.

This trial and the twelve-patient phase 1 study of cemiplimab in kidney transplant recipients are, between them, almost the whole randomised and prospective evidence base for a group that has up to a hundredfold excess risk of this cancer.