It’s my pleasure to report about a study which I presented at ASCO. Unfortunately it was a virtual meeting but I want to guide you through the major findings of the COMBI-AD trial which was an adjuvant trial in melanoma patients with stage 3 disease. We included stage 3a if the sentinel node micrometastasis diameter was more than 1mm, stage 3b and stage 3c and all of this was AJCC 7th edition classification for melanoma. All of these patients had a V600E or V600K mutation in the tumour and they were eligible if the resection was done less than twelve weeks before the randomisation.
Patients have been treated with either dabrafenib and trametinib at conventional doses, so a BRAF and a MEK inhibitor was combined, as it is approved for stage 4 disease compared to a placebo. We included in the one-to-one randomisation 870 patients and in the first analysis after three years we already showed that the overall survival is in a good way, it showed almost the same hazard ratio as relapsed and distant metastasis free survival. The second analysis after four years showed an update after a median follow-up, I was saying four years but to be precise it’s 44 months, that there is a confirmed relapse-free and distant metastasis free benefit. Now I was able to show the data after five years.
To say something about baseline characteristics, all of this was well-balanced with the well-known prognostic factors across the two study arms as expected. The major finding of this clinical trial is that the relapse free survival after five years is still separated between dabrafenib and trametinib treated patients compared to placebo treated patients and the difference is maintained from year 4 to year 5. So only 2-3% of patients will have a relapse after four years and I think this is really good to say that the curves are stable. It confirms the cure rate model which was published a year and a half ago which showed a difference of 17% between the two groups. So it’s likely that we can cure the absolute number of 17% of melanoma patients in the adjuvant setting.
Right now the relapse free survival rate after five years is 52% for dabrafenib trametinib compared to 36% for the placebo group. The relapse free survival benefit appears across all subgroups which have been evaluated which is a good sign – it’s not just one group, it’s all groups which may have a benefit. We did a subgroup analysis in particular for stage 3a with a hazard ratio of 0.61, for stage 3b it was a hazard ratio of 0.50 and for stage 3c, the group with the highest risk for a relapse, the hazard ratio here is 0.48. You see that this is very much the same, in the same ballpark.
Also we showed an update on AJCC 8th edition and the translation of the data into the new classification. Here the stage 3a patients are no longer statistically significantly benefitting from dabrafenib trametinib compared to placebo but this is because the group of stage 3a patients is only half of the size compared to the 7th edition of the melanoma classification. So the number of relapses is very low in both groups but all the other groups, stage 3b, c and d, are benefitting with clinically significant results.
Distant metastasis free survival after five years, 65% compared to 54%, corresponding to a hazard ratio of 0.55, another very good result. I need to say that we have no update on overall survival; this will be shown in the very final analysis which is scheduled in about two years, it’s an event driven analysis. There is no update on toxicity evaluation simply because all patients terminated the treatment a long time ago. The treatment was just for one year and we have the five year observation period right now. Therefore I can only conclude that there is a maintained benefit in relapse free survival, that we are likely to cure patients with dabrafenib and trametinib in the long run. I think this is the major finding of the clinical trial I presented. I’d like to thank you for listening and all the best for you.