ESMO 2025 | Comparative outcomes of ipilimumab & nivolumab dosing in melanoma

So at ESMO this year we are presenting a study where we compared two different dosages of ipilimumab and nivolumab in metastatic unresectable melanoma. So the background to this is that already in 2016 we started to use combination therapy with these drugs and this was based on the positive findings from the Checkmate 067 study. But then in 2018, there was another study, Checkmate 511, that showed when flipping the doses, that is giving instead of three milligrams of ipilimumab per kilogram, there was one milligram of ipilimumab per kilogram and this study it showed that the traditional dose had more immune-related side effects and significantly more so it also showed that looking at the efficacy and the survival there were no significant differences but since this study was not designed as a non-inferiority study this dose was never approved by regulatory authorities. So in Sweden we had concern regarding the toxicity from the traditional dose so from this time point 2018 and onwards we started to implement this dosage and it has since been in free use for advanced unresectable melanoma. So from the regions of Stockholm and region of Gothenburg, we did a population-based study where we included all patients that had been treated with ipilimumab and nivolumab for this indication and so we included 399 patients and the follow-up was 42 months and 209 had the flip dose and 199 had this traditional dose and there were some baseline differences such as those with traditional dose being somewhat younger and having more advanced disease. But when we adjusted for multiple factors, including the age of the patient, ECOG stage, and also the LDH, the disease stage, and numbers of sites of metastasis, we still found that both the overall survival and the progression-free survival was highly significant with an HR of 0.59 for the progression-free survival and 0.67 for overall survival. And also when looking at different subgroups, we found actually that the flipped dose had better efficacy. And this was also true for those with more advanced disease and also those with brain metastasis and even those with more high burden disease in the CNS and also symptomatic patients needing corticosteroids. And when we’re looking at the side effects, like in this Checkmate 511 study, we found that significantly more immune-related side effects with the traditional dose being more than 50% with the traditional and 30% with the flipped dose. And also when we saw how much treatment they had received we saw it was significantly more patients that received all four courses of ipilimumab and nivolumab with the flipped dose and also significantly more that started the maintenance nivolumab therapy. What are the reasons why we see this as an even better outcome with the flipped dose than in the Checkmate 511 study? In this study we had 360 patients and the median follow-up was 28 months is incorrect it was actually 90 months for the checkmate. But of course our study is a retrospective study, still it’s the largest real-world study looking at this. There hasn’t been any study like this before and here we leverage on that actually in Sweden we use this therapy more than I think you have been using in other countries but we think that for example in Checkmate 511 we saw that those patients that had ECOG one patients with ECOG more than that were not included in this study they actually seem to be benefiting from the flip dose and in the real world it could be that our, they are not as fit as in clinical trials. And in this setting, it could be better. And probably as the patients then are getting more treatment, more courses of therapy. But I think that at least if we see that this treatment is as good as with the traditional, that sparing the patients from all these side effects is definitely something that I think is supporting the more broader usage of this treatment.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.