Dr. van Akkooi: In this COVID-19 pandemic, we’ve been facing a lot of changes to our practice and I’m interested to hear what your take is on what the effects have been for the use of adjuvant therapy? Are there changes in the indication or changes in how you deliver that treatment to the patients?
Dr. Eroglu: I think for our patients with melanoma with a lower risk of relapse, so for example, our patients with stage III A melanomas per AJCC version 8, where we’ve already been rather ambivalent on whether to offer them adjuvant treatments, where the data hasn’t been as clear-cut on the benefit of improving relapse with adjuvant immunotherapies or target therapies...I think in this situation, we may actually lean more towards just continuing those patients on surveillance as opposed to starting them on an adjuvant systemic treatment. For our patients where we do things, there is a role for consideration of adjuvant systemic therapy, and certainly for patients we may see with stage IIIC or with IIIB melanomas post-surgery, our practice has been to still offer those patients adjuvant treatment. In terms of…when to start, based on the published data, generally we have up to about 12 weeks post-surgery, so potentially it may be appropriate, getting to where the patient is post-op, to slightly delay the start of an adjuvant treatment as needed to conserve resources, or if the patient’s not quite comfortable coming back to the clinic to start a treatment, but generally trying to keep within that 3-month time frame post-op to start an adjuvant regimen, if possible.
In terms of the adjuvant treatments themselves, for our patients with BRAF wild-type melanoma where essentially our options are limited to anti-PD1 therapies, typically our practice has favored consideration of adjuvant nivolumab given at the 480 mg per q 4-week dosing, just because it’s the less frequent visits as opposed to 240 mg every 2 weeks or the pembrolizumab 200 mg every 3-week dosing. So I think we’ve continued to offer the patients adjuvant nivolumab, but at the 480 q 4 weeks, essentially minimizing the number of visits that they have to make to our infusion center, and the blood draws that go along with that, and generally the clinic visit that has to accompany that, so essentially coming once a month for the treatments. I know some practices, and I think this regimen is only approved in Europe, have been using pembrolizumab at an every 6-week dosing. I think it’s 400 mg every 6 weeks. We don't in the United States yet have that dosing FDA approved, pembro…the q 6-week dosing...although, I think could you still use it that way? Possibly, and certainly I think in parts of the world where the q 6-week dosing of pembrolizumab is approved, I think that’s certainly also a consideration to use in the adjuvant setting in terms of decreasing the necessary visits into the clinics even further.
For the patients with BRAF V600 mutant melanoma, in the adjuvant setting we kind of have a couple of choices there. Potentially, the patients could get either adjuvant anti-PD1 therapy or BRAF MEK inhibitor therapy. Technically, the combination approved there is dabrafenib and trametinib, although if you have any issues with not having access, could you substitute the other BRAF MEK inhibitors? Probably. In terms of trying to decide... we’ve never had, obviously, any head-to-head trials in the adjuvant setting with BRAF MEK inhibitors versus anti-PD1 therapy...but perhaps in discussing the side-effect profiles with the patient, maybe you could consider BRAF MEK inhibitor therapies a little bit more in this situation given that they’re…oral regimens. You could prescribe the medication and then perhaps do a follow-up...on side effects, via telemedicine if possible, just to make sure the patient’s tolerating the treatment well. Potentially, they could even get blood work, if necessary, even through a local lab as opposed to coming into the clinic. Utilizing the BRAF MEK inhibitors in the adjuvant setting may decrease, again, the number of visits that a patient has to make into the clinic as opposed to the anti-PD1 therapy, where obviously they have to come in and generally spend a couple of hours between labs...getting the actual infusion itself.
Dr. van Akkooi: Well, Zeynep, that’s great because you've covered a lot of stuff about the time interval between surgery and starting an adjuvant treatment, the considerations for oral versus IV, the frequency of the dosage, also how to deal with visits. What has your experience been in terms of what have patients opted for? Do you see more patients now opting for oral adjuvant therapy, and do you see any changes in your practice, like you said, with more telemedicine consultations rather than real physical ones that you've been used to in the past?
Dr. Eroglu: Right. Just to address the telemedicine, I think at our institution, and I’m sure others, there’s been this exponential increase in the number of telemedicine visits that we’ve been doing. I think everyone’s been surprised on how just seeing the change overnight. I think a lot of our patients have been comfortable with that, and it can be especially optimal for patients who are on oral regimens, where we’re just having a discussion about how are you tolerating it, how are you feeling. We can have that discussion over telemedicine. Some of our patients who may be on surveillance after potentially finishing adjuvant systemic regimens, sort of the longer-term follow-up patients who are...years out from their surgeries, oftentimes those patients will get scans done, which we’ll discuss in person, but the telemedicine potentially...given how far they live, they may get scans done locally, and then we may review those via telemedicine with the patient and have those discussions, which patients have liked. Alternatively, of course, depending on the situation, could you even delay the scans, you know, 3 to 6 months, as appropriate, depending on the stage of the patients and how far, are they 2 years out, 4 years out, etc.? I think bottom line is that telemedicine’s been increasingly utilized for more and more of our visits.
The patients who have to come in regardless, for the immunotherapy regimens, generally those patients they’re in the clinic anyway, we will opt to see in person. With the rest of your question on if the patients have preferred more the BRAF MEK inhibitor therapies, I think some of them, I have noticed a little bit more who like the idea of just having the medications that they can take at home, and then [they] potentially call us or follow up with telemedicine to discuss the side effects. I think one concern that was already brought up is when we mention the possibility of the drug-related fevers, specifically with dabrafenib and trametinib in the adjuvant setting, and a couple of my patients have been concerned with that. But again, as we would do anyway, we do have a very thorough discussion of the side-effect profiles of the immunotherapies and the targeted therapies with our patients who start it.
Dr. van Akkooi: To add one more question to that, in terms of the algorithms to deal with adverse events, either immunotherapy or targeted therapy, have you adopted any changes in the way you would approach that, or are you still using the algorithms as we all used before the COVID pandemic?
Dr. Eroglu: Right. It’s been, for us, similar in terms of…the recommendations we’ll give to our patients. In terms of...when to call us when they have side effects, and in terms of how to manage with them, obviously, with immunotherapy side effects we do have to utilize corticosteroids often, which in a pandemic can lead to a little bit of concern with high doses of steroids, and potentially immunosuppressing, and so that makes them more susceptible to infections. There’s certainly some concern with that, but when necessary we do still prescribe high doses of prednisone and just monitor appropriately and give warnings, just to be very aware that they are immunosuppressed. So in terms of the dosing of prednisone, we may start with 1 mg/kg, 0.5 mg/kg, etc. Can we, when possible, try to start with the lower dose of corticosteroid or try to maybe taper a little bit faster, if feasible? Definitely, but ultimately, unfortunately, corticosteroids are sort of the go-to to manage a lot of the more significant side effects of immunotherapy drugs. It’s been hard to try to get away from that, even in these circumstances.