T-VEC Data in the Neoadjuvant Setting in Melanoma

Transcript:Robert H.I. Andtbacka, MD, CM: I think, also for this, we have additional neoadjuvant therapies, as well, that we are doing, including therapies with oncolytic viruses that we’re injecting. One of those studies is using talimogene laherparepvec, also known as T-VEC. T-VEC has been shown, in a randomized study, to be beneficial for patients with unresectable melanoma, specifically patients who have this early disease with the in-transit lesions or who have lymph node metastases or stage IV M1a, which are distant lymph nodes—so, they’re distant subcutaneous metastases. So, in that study, patients who were treated with T-VEC had a 59% lower risk of developing distant disease to lungs, liver, and other areas compared to the control arm, which was GM-CSF (granulocyte-macrophage colony-stimulating factor), leading us to believe that some of these oncolytic immunotherapies may be able to be used in this early setting of patients to try to prevent them from developing recurrence and distant disease.

Now, that was in unresectable patients. So, we’re now taking just the patients that have resectable disease and asking the same question: can we then treat these patients with T-VEC for 3 months and then do surgery versus doing surgery up front? And do we see a difference, then, in the risk of recurrence for these patients? Again, we don’t know the answer to that. This is done in a clinical trial.

I really want to emphasize that all of this really should be done in the clinical trials in order to get appropriate data and be able to follow these patients appropriately. I think it is very exciting for us in melanoma that we now have therapies that we can take early on and really use in the setting for these patients that have a very high risk of recurrence of their disease. Now, the question then becomes, Georgina, if you have these patients that you treat on a clinical trial with a BRAF/MEK combination and they have a complete response, do we still have to do surgery for these patients?

Georgina Long, MD: Absolutely. It’s a clinical trial, and without the pathological assessment, we can’t actually say whether they’ve had a pathological complete response. And that is the endpoint of interest. We know from the metastatic setting that patients who undergo a complete response there do better long term. We need to assess this and get the data around that. They must go on to have their surgery, even if there’s nothing to see radiologically, so that we can see the microenvironment and get a full assessment pathologically. And in terms of treatment beyond the surgery, just for equipoise with the current clinical trials or the clinical trials that have been opened and now closed, we continue treatment for 12 months.

Robert H.I. Andtbacka, MD, CM: And I guess that’s also something that we need to determine as well—the need of that additional therapy, the adjuvant therapy—through clinical trials. I think that the advantage of neoadjuvant therapy, such as this, on a clinical trial is that it really gives us the opportunity to study the effects that these drugs have on the tumor, on the immune system, and on the tumor microenvironment, and probably for us to gain a better understanding that we sometimes can do this in patients with stage IV metastatic disease. I think that this really will help us, not only in these patients with stage III disease that we’re treating, but also later on in patients with stage IV disease as well.

Transcript Edited for Clarity