The addition of the mTORr inhibitor, Everolimus, to consolidation therapy in acute myeloid leukaemia: experience from the UK NCRI AML17 trial

As part of the UK NCRI AML17 trial, adult acute myeloid leukaemia patients in remission could be randomised to receive the mTOR inhibitor everolimus, sequentially with post-induction chemotherapy. Three hundred and thirty-nine patients were randomised (2:1) to receive everolimus or not for a maximum of 84 days between chemotherapy courses. The primary endpoint was relapse free survival (RFS). At 5 years there was no difference in Relapse Free Survival (29% vs 40%; OR 1.19 (0.9-1.59) p=0.2), cumulative incidence of relapse (60% vs 54%: OR 1.12( 0.82-1.52): p=0.5) or overall survival (45% vs 58%: OR 1.3 (0.94-1.81): p=0.11). The independent Data Monitoring Committee advised study termination after randomisation of 339 of the intended 600 patients due to an excess mortality in the everolimus arm without any evidence of beneficial disease control. Dose delivery of everolimus was variable, but there was no evidence of clinical benefit in patients with adequate dose delivery compared with no treatment. This study suggests that the addition of mTOR inhibition to chemotherapy provides no benefit. Clinica Trial: ISRCTN55675535.