{"entity":{"id":"tumorapa","kind":"trial","name":"TUMORAPA (switching from a calcineurin inhibitor to sirolimus after a transplant skin cancer)","aka":["TUMORAPA","TUMORAPA 1"],"tldr":"A person with a transplanted kidney who has had one skin squamous cancer will usually get more. Swapping one anti-rejection drug for another roughly halved the number who got another cancer, but it made people unwell often enough that a quarter stopped the new drug.","summary":"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.\n\nSurvival 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squamous cell carcinomas developed in 14 of 64 patients (22 per cent) on sirolimus, six of them after the drug had been withdrawn, against 22 of 56 (39 per cent) on calcineurin inhibitors, with a median time to onset of 15 against 7 months (p=0.02) and a relative risk of 0.56 (95 per cent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.\n\nThe 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.\n\nThis 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.","status":"positive","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT00133887","url":"https://clinicaltrials.gov/study/NCT00133887"},{"label":"Primary report (New England Journal of Medicine 2012)","url":"https://doi.org/10.1056/NEJMoa1204166"},{"label":"Primary report on PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22830463/"}],"tags":[],"related":[],"cancers":["cutaneous-scc","skin-cancer"],"sections":[],"technologies":["chemoprevention"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["skin-cancer-after-organ-transplant","field-cancerisation"],"trials":["cemiplimab-kidney-transplant-cscc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00133887","phase":"3","setting":"Kidney transplant recipients taking calcineurin inhibitors who had already had at least one cutaneous squamous cell carcinoma: substituting sirolimus for the calcineurin inhibitor against maintaining the existing treatment, with survival free of squamous cell carcinoma at two years as the primary endpoint","sponsor":"Hospices Civils de Lyon","result":"New cutaneous squamous cell carcinoma in 22 per cent of patients switched to sirolimus against 39 per cent continuing calcineurin inhibitors (relative risk 0.56, 95 per cent confidence interval 0.32 to 0.98), with 23 per cent stopping sirolimus for adverse events.","yearReported":2012,"enrolled":120,"enrolledBasis":"randomised","enrolledNote":"120 kidney transplant recipients were randomised, 64 to sirolimus and 56 to continued calcineurin inhibitor treatment; the ClinicalTrials.gov record NCT00133887 gives an enrolment of 77.","outcomes":[{"endpoint":"New cutaneous squamous cell carcinoma","primary":true,"unit":"%","arms":[{"name":"Switch to sirolimus","n":64,"value":22,"note":"14 of 64 patients, 6 of them after sirolimus was withdrawn; median time to onset 15 months"},{"name":"Continue calcineurin inhibitor","n":56,"value":39,"note":"22 of 56 patients; median time to onset 7 months"}],"p":"0.02","source":"https://doi.org/10.1056/nejmoa1204166"},{"endpoint":"Serious adverse events per patient","unit":"events per patient","arms":[{"name":"Switch to sirolimus","n":64,"value":0.938,"note":"60 serious adverse events; 23 per cent discontinued sirolimus"},{"name":"Continue calcineurin inhibitor","n":56,"value":0.25,"note":"14 serious adverse events"}],"source":"https://doi.org/10.1056/nejmoa1204166"}],"replication":"Retrospective and registry work has pointed the same way, and mammalian target of rapamycin inhibitor conversion is in transplant dermatology guidance, but no second randomised trial of the size of TUMORAPA has been run."},"route":"/trials/tumorapa/","neighbours":{"cancer":[{"id":"cutaneous-scc","kind":"cancer","name":"Cutaneous squamous cell carcinoma","route":"/cancers/cutaneous-scc/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"technology":[{"id":"chemoprevention","kind":"technology","name":"Chemoprevention & risk-reducing surgery","route":"/technologies/chemoprevention/"}],"term":[{"id":"skin-cancer-after-organ-transplant","kind":"term","name":"Skin cancer after an organ transplant","route":"/terms/skin-cancer-after-organ-transplant/"}],"pathway":[{"id":"field-cancerisation","kind":"pathway","name":"Field cancerisation","route":"/pathways/field-cancerisation/"}],"trial":[{"id":"cemiplimab-kidney-transplant-cscc","kind":"trial","name":"Cemiplimab for kidney transplant recipients with advanced skin squamous cell carcinoma","route":"/trials/cemiplimab-kidney-transplant-cscc/"}]}}