New dexamethasone combination yields two-fold improvement in median PFS in multiple myeloma
Prof Meletios Dimopoulos - University of Athens, Athens, Greece
Can you tell us about the ENDEAVOR study?
The idea was to use as a standard bortezomib and dexamethasone, which is an established treatment for patients with relapsed myeloma, and to compare it with carfilzomib with dexamethasone. So it was a head to head comparison of two proteasome inhibitors. The patients included in the trial were patients with relapsed myeloma who had received 1-3 prior lines of therapy and these patients could have received prior therapy with bortezomib but they should have been responding to bortezomib and progressing at least six months off treatment with bortezomib. So a very large number of patients were included, 929 patients. The randomisation was stratified according to prior lines of therapy, ISS, prior exposure to bortezomib. The main finding of the study was a significant improvement in PFS, in progression free survival, in favour of Kd at 18 months versus 9 months with bortezomib. So there was a doubling of the progression free survival. Furthermore response rate was higher in favour of Kd, toxicity profile was acceptable with both arms – peripheral neuropathy, constipation and diarrhoea were common with bortezomib whereas shortness of breath, cough, pyrexia were more common with carfilzomib. Also there were higher grades of hypertension in the carfilzomib arm and a small but definite increase in cardiotoxicity in patients treated with carfilzomib and dexamethasone.
What are the clinical implications?
There are several implications. First of all, this trial will help and will expedite the approval of carfilzomib in Europe. As we know, this drug has been available in the United States for the last three years but not yet in Europe. Also, carfilzomib and dexamethasone may provide a very effective treatment for patients who have been previously treated with lenalidomide and we know that especially in the United States many patients are on lenalidomide maintenance. Thus we have another combination which appears to be very effective in the treatment of relapsing myeloma