Merrick I. Ross, MD: Decision making is always a difficult situation when patients have choices. Different oncologists may have biases as well. When the patient has a BRAF mutation, they certainly have multiple options. They could receive targeted therapy, and there’s no reason why they can’t receive immunotherapy. As a matter of fact, if you look at the immunotherapy trials in the adjuvant setting, looking at BRAF-mutated versus BRAF wild-type cases, there doesn’t seem to be an appreciable difference in the efficacy. I think the most important issue is the concern that there has not been a randomized trial that compares targeted therapy to immunotherapy in patients who have a BRAF mutation. That trial has not been done. I don’t know if it’s ever going to be done, but it seems like a reasonably good question to ask. Because of the efficacy that was seen in the BRAF/MEK trial, which was very impressive, that would be my first choice for patients who have a BRAF mutation.

There is a concern about using immunotherapy in the adjuvant setting because of potential toxicity, which can be very long-lasting. In the adjuvant setting, depending on the risk profile, many patients are already cured by surgery alone. So, there has to be a very important partnership and discussion between the patient and the treating clinician about the risk-benefit ratio. Patients who are young, who have a long time to live, and don’t have underlying comorbidities are probably excellent candidates for adjuvant therapy. Elderly patients with comorbidities may not be the best candidates. Some assessment of risk that is accurate is important for the patient to help make decisions about using adjuvant therapy to begin with, and then biomarkers can be used to help guide which therapy to use.

For patients who develop recurrence on adjuvant therapy either during therapy or after they’ve completed therapy, it’s difficult to know what the biology is on those 2 different types of patients. We don’t have enough experience yet. If the recurrence is resectable, we would probably place the patient on a neoadjuvant trial, where you probably test combinations of therapies to see what the patient’s response level is to a certain regimen. If the patient is resectable, you would then perform a standard surgical resection. I’d probably consider that same therapy that was used in the neoadjuvant setting. I’d bring it into the adjuvant setting afterwards. So, a clinical trial is probably the best option for patients who relapse either during or after adjuvant therapy.

Transcript Edited for Clarity