Dr. Eroglu: Any thoughts specific to patients with melanoma brain metastases, especially patients who may be symptomatic, and whether you may consider the ipi-3/nivo-1 regimen for them and how you may incorporate use of stereotactic radiation or surgery, if needed, and then also whether, with clinical trials, what your thoughts are in terms of if you would still consider enrolling patients on to clinical trials during this time, and kind of what your practice has been?
Dr. VanderWalde: So, those are both very important questions. I’ll start with the first one, which is what to do with patients with brain metastases? There are really sort of a couple of different scenarios that we can talk about. The first is when they have oligometastatic disease to the brain that is asymptomatic. In patients who have asymptomatic oligometastatic disease, stereotactic radiation remains, at least in my practice, the treatment of first regard, and usually, that can be done with basically a staging and single-visit approach to be able to really kind of just zap the oligometastatic disease. Following that treatment, I think that I would still recommend it be nivo-3 in that situation. It’s almost an adjuvant setting, which is why I hesitate a little bit, but in our practice, we have been giving an ipi-3/nivo-1 in those scenarios, and I think I would continue to do the same. In patients with oligometastatic disease who are symptomatic, I think it becomes very important for them to be able to get either surgery or stereotactic radiation as soon as possible, and that has not changed during the COVID pandemic. I think these patients have to be treated very rapidly before they very rapidly deteriorate.
In patients who have extensive…either unacceptable or un-radiationable disease, my general inclination is that rather than go to whole-brain radiation, it’s very important to start them on full-dose ipilimumab plus nivolumab, and especially if they’re asymptomatic in that setting. I think that that is what we would do and not treat the patients at all with stereotactic radiosurgery or whole-brain radiation in that setting. In patients who have lots of metastatic disease in their brain and are symptomatic, there’s no great therapy available. Unfortunately, if we ever use whole-brain radiation therapy in combination with ipi/nivo that would be an experimental and probably not super effective place to do that.
In terms of questions of clinical trials, a lot of different centers are doing this in a different way. My general approach is that, especially in metastatic disease, a clinical trial represents the best treatment option available for a patient. Whenever possible, putting a patient on to a clinical trial or keeping the patient on the clinical trial that they’re already on really is paramount. That said, not every clinical trial is designed equally. There are some clinical trials that continue to have placebo controls or best-practice controls, and I think the decision really needs to be made on a patient by patient, risk by risk-benefit, but my general bias is to offer patients clinical trials in this scenario and to limit the number of visits. Both IRBs and clinical trial sponsors in the industry have been very open to allowing for minor deviations or calling what otherwise would have been major deviations minor deviations in the setting of COVID, allowing for consent done over the phone while the patient has a copy of the consent form, signs it themselves, and then faxes it in or mails it in or even scans it in so that the witness who was able to watch them do it can then sign a hard copy. [That] has been something that routinely by most IRBs has been allowed for the consenting process. Screening windows have been extended, and non-treatment visits have been able to be done through telemedicine. So I think the clinical trials have adapted relatively quickly and appropriately to the COVID pandemic, and I think it continues to be generally safe and hopefully efficacious to continue to treatment patients on them.
Dr. Eroglu: Yeah, I would absolutely echo what you said with regards to clinical trials. At our institution, we’ve continued a lot of our trials in the metastatic setting as well, and as you said, a lot of the study sponsors have been very quick to adapt to the situation, and I would agree that it should still remain an option for patients when possible. Ari, was there anything else you wanted to focus on?
Dr. VanderWalde: I wanted to just give a disclaimer that the clinical trials that I’m really touting are in the metastatic setting. It becomes a much more difficult proposition to weigh risks and benefits in the adjuvant setting, especially when looking at randomized control trials, where the patients have an equally likely opportunity to be able to get either standard-of-care therapy or placebo. There are a couple of trials ongoing in stage II disease, for example, that are randomized to placebo. I tend to err a little bit more on the side of not putting patients on clinical trials especially in a placebo-controlled trial, because it’s really almost impossible to limit the total number of visits and keep them down to what would have been standard of care in those types of trials. I also am a little bit concerned about translational medicine, on-study biopsies, pre-study biopsies that are not necessary for randomization or stratification of trials, and really doing whatever is possible to limit those because those really are biomarker studies that are embedded into what otherwise is a therapeutic study. So we’re trying to limit the number of biopsies that patients have to undergo on clinical trials as well, and again, sponsors have been relatively understanding of that.
I hope that everybody’s able to stay safe out there. These are unprecedented times that none of us have seen in our careers before, and we’re all trying to do the best we can.