The SECOMBIT trial is very interesting because it included a sandwich arm where patients got eight weeks of targeted therapy before crossing over to get immune therapy without having disease progression. And in that study, it showed that immunotherapy first was better than targeted therapy, but it was interesting in the group of patients with an elevated LDH, there appeared to be an additional benefit by giving eight weeks of targeted therapy before switching to immune therapy over starting with immune therapy...
The SECOMBIT trial is very interesting because it included a sandwich arm where patients got eight weeks of targeted therapy before crossing over to get immune therapy without having disease progression. And in that study, it showed that immunotherapy first was better than targeted therapy, but it was interesting in the group of patients with an elevated LDH, there appeared to be an additional benefit by giving eight weeks of targeted therapy before switching to immune therapy over starting with immune therapy. And so that is potentially a population who might get targeted therapy for a short period of time first. We are also looking at biomarkers in the DREAMSeq trial. And as I presented previously, patients with aggressive disease as marked by an angiogenesis high signature might be a group of patients who should get targeted therapy first. Not because they do better with targeted therapy than immunotherapy in the front line, but because they do better with second line immunotherapy than they would with immunotherapy in the front line. And the TRIDENT trial looked at triplet therapies, and we see with all the triplet studies that the two-year and subsequent progression-free survival curves are lower than the five-year immunotherapy alone progression-free survival curves from things like 067 and from the DREAMSeq trial. And those patients have already exhausted their BRAF/MEK option, and the patients on immunotherapy alone can still get BRAF/MEK. So it suggests that adding PD-1 to targeted therapy compromises the overall survival benefit of the trial. A lot of this data will be presented at the ASCO webinar looking at skin cancer results, which will be on June 18th of this year.
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