Targeted- vs Immunotherapy in BRAF+ Stage III Melanoma

Medscape

25-06-2025

This transcript has been edited for clarity.
Hello, everybody. My name is Teresa Amaral. Welcome back to this Medscape melanoma series. In the past four episodes, we talked a bit about adjuvant therapy in melanoma — what we have in terms of immunotherapy, the aspects that we need to consider, relapse-free survival data, distant metastasis-free survival data, and the absence of overall survival data.
Today I'm going to discuss a little bit of the controversy that is ongoing in terms of what is the best therapy for patients who have a stage III melanoma and BRAF mutation. What kind of therapy in the adjuvant setting should we give to these patients? To address this question, we have recently published a review in terms of real-world data comparing these two therapies.
Why did we do that? First, because these two therapies are approved for patients who have a BRAF mutation and there are no head-to-head comparisons that have been performed in clinical trials. Most likely, they will not be performed in the future because both therapies are approved in stage III; therefore, there is not really a big interest from the companies to perform this comparison in a head-to-head study.
Because of that, we used a previous analysis based on a mathematical form where we visually compared the survival curves that have been published in real-world cohorts. This type of visual comparison has been published before to analyze stage IV systemic therapy, specifically immunotherapy and targeted therapy.
The first publication was in 2017 in the European Journal of Cancer and the second was published in 2018 in the same journal. Basically, we used this strategy to also visually compare the different curves for immunotherapy and targeted therapy in stage III for patients with BRAF -mutated melanoma.
We searched PubMed and other databases for articles that have published real-world data in this setting. We were able to include more than 3000 patients with a median follow-up that goes between 11 and 33 months.
Approximately half of the patients, 57%, had a BRAF mutation. From these, approximately half of the patients had received treatment with a BRAF/MEK inhibitor, which gives us, at least from my point of view, a very good overview of the outcome of these patients treated with targeted- and immunotherapy.
In total, we were able to retrieve 20 plus 32 publications. After the first review, we had 29 publications, excluding the duplicates. With further selection, we were able to have a total of eight studies that were included in this real-world analysis.
We performed, as I said, a visual comparison between the two types of therapies, so immunotherapy and targeted therapy. The first analysis we performed was in terms of relapse-free survival. Here, we included nine publications in total. We see the relapse-free survival curves after 2 and 3 years, but from the very beginning, after 1 year, a difference that is visually better for targeted therapy.
In this real-world data analysis, we saw that patients treated with targeted therapy seem to have a better benefit that is maintained, at least at 3 years, which is the last time that we performed this visual comparison.
We also looked into the survival curves for immunotherapy and for targeted therapy in the different studies to make sure that patients treated with either therapy did not have a significantly different survival outcome.
The curves are presented in the publication, and you can see that there is a significant overlap between the survival curves, showing that the patients treated in the different studies had a similar outcome. This is true both for targeted therapy and for immunotherapy.
Why is this relapse-free survival analysis so important and why did we do this comparison? Both therapies were initially approved based on the relapse-free survival benefit that they showed for immunotherapy, and as we discussed in the previous episodes, there is still no overall survival benefit available. For targeted therapy we have overall survival benefit, but approval was based on relapse-free survival benefit.
When we looked into the distant metastasis-free survival, we also saw that for patients treated with targeted therapy, the benefit was higher than for patients treated with immunotherapy. Here, we only had data from two publications; therefore, we cannot really have sound conclusions on what is better in terms of treatment for patients with BRAF -mutated stage III melanoma.
Then we tried to do the analysis also for overall survival, but here again, we only had data from three publications; therefore, the comparisons cannot really be considered because the number of patients is quite low. Still, there is an overlap here, and the difference that we saw before in terms of benefit for distant metastasis-free survival and relapse-free survival favoring targeted therapy was not seen in this overall survival comparison.