Evolving Approaches in Melanoma Treatment

Medscape

a day ago

This transcript has been edited for clarity.
Hello, everybody. I am Teresa Amaral, head of the Skin Cancer Clinical Trials Center at Tübingen University Hospital in Germany. I'm here directly from ASCO 2025 to discuss with you a couple of works that have been presented here and I think are important for you to know about and discuss.
We are already in June, but last month was Melanoma and Skin Cancer Awareness Month. I think it's interesting that one of the posters and one of the works that was selected to be discussed here was associated with strategies and interventions to prevent melanoma and other skin cancers — namely, works and interventions that have been done in kids and young adults in order to prevent ultraviolet exposure.
This is something that you don't see often. It's talked about frequently, but these kinds of interventions are not very common. It's very interesting to see that this has been selected to be discussed here.
Well, that was part of the prevention, and now we go to early-stage melanoma. As you can imagine, and as you probably know, the majority of the patients that are diagnosed with melanoma are actually diagnosed at an early stage. This means stage I and stage II.
Being the majority of the population that is diagnosed with melanoma, it's also the population for which we don't have any approved therapy, especially until stage IIA. What can we do for these patients?
There have been a couple of works presented here at ASCO using artificial intelligence to look at slides from patients and from primary tumors of patients diagnosed with early-stage melanoma. Actually, these have been pretty promising for predicting the risk for recurrence of these early-stage patients. In this transcript to accompany the video, we've linked the posters and you can get more information if you want to look into more detail at the data that have been presented.
Another work that I would like to call your attention to, for which I definitely have some bias because it's the poster that I presented here, is a gene expression profile also using the primary tumor of patients diagnosed with early-stage melanoma — so stage I and stage II. The majority of the patients had stage IA disease.
We looked into the primary tumors and tried to identify the patients that are at higher risk of developing a recurrence without having the information of the sentinel lymph node biopsy. Looking into those who have high risk is one of the ways to look into this population, but also looking into those who have low risk and can safely forgo other evaluations or other interventions such as further follow-up, skin checks, ultrasounds, blood tests, and so on.
Then moving into the adjuvant setting, where we already have some therapy that is reimbursed. For stage II, we have immunotherapy. For stage III, we have immunotherapy and targeted therapy for the patients with BRAF mutation.
Some of the data that has been presented here are looking into different ways of not only clinical data, but also gene expression profile, next-generation sequencing, and other assays such as circulating tumor DNA, and combining all this information to try to understand who are the patients that will have a recurrence, and if we can see it from the very beginning in those patients who received adjuvant therapy.
There were a couple of posters looking into this, showing that in principle, and based on these data, we might not have only one biomarker that can tell us which patients are those who, despite therapy, will recur, or which patients who, under therapy, will have a benefit.
Interestingly enough, we also have other trials being presented on Tuesday, and we'll have another session looking into detail at trial data on targeted therapy in the adjuvant setting — the COLUMBUS-AD study— and also a negative trial, the Bristol Myers Squibb trial RELATIVITY-098, which looked into programmed cell death protein 1 (PD-1) vs PD-1 plus lymphocyte activation gene 3 in patients in stage III. I think this is a very important trial, and it's important that these negative trials are also presented and are discussed so that we can understand which patients really don't benefit and what we can use from these trials to move the investigation forward.
Another interesting poster that was presented here is looking into patients receiving adjuvant therapy with immunotherapy or targeted therapy if they have a BRAF mutation. Why is this poster interesting? I would say that there are some conflicting data on what type of therapy you should use in the adjuvant setting if the patients have a BRAF mutation.
There are some retrospective data showing that targeted therapy upfront might be better. The poster presented here shows that immunotherapy actually seems to do better, although the majority of the patients were indeed treated with immunotherapy, not targeted therapy.
I think real-world data and retrospective data are more important every day because I don't expect to have any trial in the future looking into adjuvant targeted therapy or immunotherapy for patients with stage III melanoma. Besides the BRAF mutation, we will definitely need other biomarkers that will help to guide our decisions for patients who have BRAF -mutated stage III melanoma.
Moving into the advanced setting, the most important questions that we want to get answered are not what we should use in first-line therapy because this is, I would say, pretty clear for the majority of patients.
We have data from the SECOMBIT trial. We have data from the DREAMseq trial saying that patients will probably benefit more from immunotherapy upfront, even when they have a BRAF mutation. Very particular patients will be candidates for having targeted therapy upfront, as the majority of them will receive immunotherapy.
This is exactly what is going to be presented on Tuesday from the DREAMseq study. The data will show that after 5 years, there is almost twice as high overall survival rate in patients that started with immunotherapy and three times better progression-free survival for patients that started with immunotherapy as compared to targeted therapy alone.
There are some nuances from this trial because not all the patients that started with immunotherapy or targeted therapy did the crossover; many had brain metastases, which was one of the exclusion criteria for the crossover. Still, it shows that for the majority of the patients, you should start, if possible, with immunotherapy in the first line.
It will be interesting to understand what to do for patients for whom we don't have a benefit using PD-1 therapy. There come the second-line therapies and more, I would say, experimental data on other strategies that include cell therapy and tumor-infiltrating lymphocyte (TIL) therapy.
There have been some data presented in a poster, showing that patients who received TIL therapy have a good long-term outcome 5 years after this therapy. This might be a therapy that could possibly be given to a specific subgroup of patients in a very selected population.
Also interesting would be to look into the same strategy without using the lympho depletion that is normally associated with this type of therapy and the interleukin-2 that is also given because this is, first, one of the limitations to select the patients that will get this therapy, and second, these two therapies are responsible for the majority of the toxicity that we see with this therapy. These are really interesting data to see how we can bring this therapy to our patients, but also how we can do it with reducing toxicity.
Finally, one of our other treatments that has been discussed here and will also probably come in our future discussions are treatment-directed therapies — so local therapies such as injection therapies and viral therapies. These have been coming on the scene again, with new data from a different type of viral therapy but also with a combination of PD-1 therapy, which I think is quite interesting because they are looking into patients that really didn't benefit from PD-1 therapy.
For the future, these would be my two or three populations where I think we need more data and we should definitely invest more in future trials. First, for early-stage trials, and again, looking into trials that are biomarker-selected. I don't think we can go on doing adjuvant trials in all the populations of patients with stage II and stage III.
Second, for patients who did not benefit from PD-1 therapy in the advanced setting, but also those who received PD-1 in the adjuvant setting and did not benefit from that. And third, for patients with brain metastasis, which is obviously a difficult-to-treat population for which we don't have many options.
Finally, there were some posters also analyzing treatment for patients with acral melanoma and mucosal melanoma, which again are populations that normally are excluded. It's nice to see that some companies are still investing in that.
Also, there are some retrospective data showing that, despite the fact that patients do not benefit as much as those with normal cutaneous melanoma, there is still plenty of space to investigate new treatment avenues for this population that normally is excluded from clinical trials.
This was my summary from what we know so far from ASCO 2025. I'll get back to you with a second take on this interesting meeting when we have the late-breaking abstracts presented in the rapid oral communications, and also in the oral communications, which I think might also come in handy when you want to decide what to do with your patients in the clinics next week.
I hope you enjoyed the meeting, and I'm looking forward to seeing you again soon. Thank you.