This transcript has been edited for clarity.
Welcome back to this third episode on biomarkers. We will discuss how and if we can use biomarkers in our daily practice.
In the first episode, we looked into what a biomarker is; the characteristics of a biomarker; specificity and sensitivity, and why they are important for deciding the type of tests that we would like to have; and the information that these tests give to us.
In the second episode, we looked into biomarkers that can be used in early-stage melanoma, using the primary tumor alone or using both the tumor and the patient's characteristics. We discussed gene-expression profiles and also nomograms. We also discussed the fact that [going forward] we will need to select patients to receive therapy and not continue to do trials with all-comers.
Now I would like to give you some reasons why we should not treat patients with early-stage melanoma — in this case, stage II. Then I would like to discuss why it would be a possibility to treat these patients.
Why not treat? One reason is because we clearly see in the data from the adjuvant trials in stage II that a significant proportion of patients who are treated do not benefit from the drug. We also see patients who have received therapy that did not need therapy, because they will not have any recurrence.
The percentage of patients that really benefit from this therapy is quite small. We really need to identify the patients to whom we need to give therapy because they will have recurrence and they benefit from the therapy because the recurrence will not exist, or exist later on.
The fact that the patients have a benefit in terms of relapse-free survival and also distant metastasis-free survival is important, but we need to understand that in the long run, if there is no benefit, this needs to be discussed with the patients.
What do I mean by "long run"? If there is no overall survival benefit, or if this relapse-free survival and distant metastasis-free survival benefit do not correlate with the overall survival benefit, the patients need to be aware of that, especially because of the toxicity that is associated with these kinds of therapies.
Potential toxicity in some cases, like the immunotherapy that is offered in stage II, might lead to long-term toxicity that will be lifelong — for example, hypophysitis or diabetes. This is important when we are discussing these therapies with our patients.
Of course, remember that there is a relapse-free survival benefit, but we don't know which patients will benefit from this, nor if these patients will not need therapy. I mention the distant metastasis-free survival benefit because it exists. But especially for immunotherapy and in stage II, there are no overall survival data so far, and it's planned quite later in the future. We need to discuss this with patients and they need to be aware that the benefit that we see, or that potentially can exist, might also be associated with some toxicity.
Another point that we need to discuss with patients is that in other settings, especially in stage III, we have not seen a correlation between distant metastasis-free survival and overall survival with all therapies.
Even if there is a distant metastasis-free survival or a relapse-free survival benefit, the overall survival in some cases is nonexistent. That means, if we take the example of stage III or even other pathologies — again, we are talking about stage II in our discussion — it might be that this benefit in terms of relapse-free survival and distant metastasis-free survival does not translate in overall survival benefit.
As I mentioned before, toxicity might be lifelong and also represent, in some cases, a substitution with medication. The patients need to be aware of this potential issue with systemic therapy.
Of course, we need to consider the benefits that I mentioned. And the fact that the patients do not have a relapse, meaning they are disease free, is an important aspect. Being tumor free is completely different from having a disease that has a local recurrence or a distant metastasis that is treated with systemic therapy. All these aspects in terms of benefits and risks need to be clearly stated when we are discussing therapies with patients in this context.
What also needs to be considered, and which we need to understand, is that when patients have recurrence, at least based on the data that we have from the studies that looked into therapy in stage II, the majority of patients who didn't receive therapy in the placebo arm actually recurred with distant metastasis.
This is, of course, a burden that the patients will have, and it's important information that we need to convey to the patients when we are discussing adjuvant therapy.
All of these data need to be combined and put in context with the patient's preferences and probabilities. It needs to be a shared decision, considering that we started by saying that, currently, we really don't have a biomarker that has been tested prospectively and that allows us to understand which patients will benefit from the systemic therapy that we are offering at this time point.
COMMENTARY
Who Really Needs Treatment? Navigating the Biomarker Challenge in Early-Stage Melanoma
DISCLOSURES
| March 27, 2025This transcript has been edited for clarity.
Welcome back to this third episode on biomarkers. We will discuss how and if we can use biomarkers in our daily practice.
In the first episode, we looked into what a biomarker is; the characteristics of a biomarker; specificity and sensitivity, and why they are important for deciding the type of tests that we would like to have; and the information that these tests give to us.
In the second episode, we looked into biomarkers that can be used in early-stage melanoma, using the primary tumor alone or using both the tumor and the patient's characteristics. We discussed gene-expression profiles and also nomograms. We also discussed the fact that [going forward] we will need to select patients to receive therapy and not continue to do trials with all-comers.
Now I would like to give you some reasons why we should not treat patients with early-stage melanoma — in this case, stage II. Then I would like to discuss why it would be a possibility to treat these patients.
Why not treat? One reason is because we clearly see in the data from the adjuvant trials in stage II that a significant proportion of patients who are treated do not benefit from the drug. We also see patients who have received therapy that did not need therapy, because they will not have any recurrence.
The percentage of patients that really benefit from this therapy is quite small. We really need to identify the patients to whom we need to give therapy because they will have recurrence and they benefit from the therapy because the recurrence will not exist, or exist later on.
The fact that the patients have a benefit in terms of relapse-free survival and also distant metastasis-free survival is important, but we need to understand that in the long run, if there is no benefit, this needs to be discussed with the patients.
What do I mean by "long run"? If there is no overall survival benefit, or if this relapse-free survival and distant metastasis-free survival benefit do not correlate with the overall survival benefit, the patients need to be aware of that, especially because of the toxicity that is associated with these kinds of therapies.
Potential toxicity in some cases, like the immunotherapy that is offered in stage II, might lead to long-term toxicity that will be lifelong — for example, hypophysitis or diabetes. This is important when we are discussing these therapies with our patients.
Of course, remember that there is a relapse-free survival benefit, but we don't know which patients will benefit from this, nor if these patients will not need therapy. I mention the distant metastasis-free survival benefit because it exists. But especially for immunotherapy and in stage II, there are no overall survival data so far, and it's planned quite later in the future. We need to discuss this with patients and they need to be aware that the benefit that we see, or that potentially can exist, might also be associated with some toxicity.
Another point that we need to discuss with patients is that in other settings, especially in stage III, we have not seen a correlation between distant metastasis-free survival and overall survival with all therapies.
Even if there is a distant metastasis-free survival or a relapse-free survival benefit, the overall survival in some cases is nonexistent. That means, if we take the example of stage III or even other pathologies — again, we are talking about stage II in our discussion — it might be that this benefit in terms of relapse-free survival and distant metastasis-free survival does not translate in overall survival benefit.
As I mentioned before, toxicity might be lifelong and also represent, in some cases, a substitution with medication. The patients need to be aware of this potential issue with systemic therapy.
Of course, we need to consider the benefits that I mentioned. And the fact that the patients do not have a relapse, meaning they are disease free, is an important aspect. Being tumor free is completely different from having a disease that has a local recurrence or a distant metastasis that is treated with systemic therapy. All these aspects in terms of benefits and risks need to be clearly stated when we are discussing therapies with patients in this context.
What also needs to be considered, and which we need to understand, is that when patients have recurrence, at least based on the data that we have from the studies that looked into therapy in stage II, the majority of patients who didn't receive therapy in the placebo arm actually recurred with distant metastasis.
This is, of course, a burden that the patients will have, and it's important information that we need to convey to the patients when we are discussing adjuvant therapy.
All of these data need to be combined and put in context with the patient's preferences and probabilities. It needs to be a shared decision, considering that we started by saying that, currently, we really don't have a biomarker that has been tested prospectively and that allows us to understand which patients will benefit from the systemic therapy that we are offering at this time point.
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
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