Panelists: Jeffrey S. Weber, MD, PhD, Laura and Isaac Perlmutter Cancer Center; Jason J. Luke, MD, FACP, UPMC Hillman Cancer Center; Vernon K. Sondak, MD, Moffitt Cancer Center; Ryan J. Sullivan, MD, Massachusetts General Hospital; Hussein A. Tawbi, MD, PhD
Jeffrey S. Weber, MD, PhD: How do you handle talking to the patient with resected stage IIIb or stage IIIc disease in the clinic who’s BRAF mutated? How do you decide whether they should get BRAF/MEK? Do they get to have dabrafenib-trametinib, or are they going to get immunotherapy? Would it be nivolumab? Would it be pembrolizumab? How do you handle that?
Jason J. Luke, MD, FACP: The first thing, again, is to make sure that you know the BRAF status. You can’t really have the conversation if you don’t know the BRAF status. When you know that, you can then approach the patient and offer them the data that we have, which essentially show equipoise between these modalities. Then it really comes down to: What are the treatment goals, and what are the various factors that are influencing the patient’s care?
A targeted therapy comes in the form of a pill. There are some up-front toxicities that are, generally speaking, manageable, but can sometimes be bit troublesome with fevers, etc. Alternatively, immunotherapy tends to be well tolerated and less frequently administered, but you need to come to the clinic for treatment. There’s a small but real incidence of irreversible toxicities, predominantly endocrinopathies. And in the younger patient, that’s something that definitely should be on the radar. This could have an influence, obviously, throughout the rest of their life, relative to fertility and so on and so forth.
These are nuanced questions, and it’s a lot for a patient to take in all this information at once. And so I really think we should also stress that this is not a question that needs to be rapidly answered in the adjuvant setting. You could have 1 or 2 visits to go through all this to help the patient, and even their family members, to make that decision about what’s really best for them.
Jeffrey S. Weber, MD, PhD: Hussein, how do you look at the differential risks and toxicities and explain that to patients—BRAF/MEK versus PD-1 [programmed cell death protein 1] blockade as adjuvant therapy?
Hussein A. Tawbi, MD, PhD: This is always a fun conversation to allow me to nerd out a little bit and tell my patients why the BRAF blockade kind of works and then how immunotherapy works. But most importantly, it’s very important to explain the characteristics and qualities of the toxicities to them. It’s a really interesting kind of differential, as Jason was alluding to. While the rates of toxicities may be different, it is the durability of the toxicity, so to speak, that actually can sometimes sway 1 patient toward 1 treatment versus the other.
With targeted therapy, 26% of patients actually end up discontinuing therapy because of toxicity. However, in those patients who discontinue because of toxicities, the toxicity basically dissipates shortly after they stop their therapy. With immunotherapy, it’s a lot lower rate of discontinuing—around 10%, 12%. However, there is a small percentage of those toxicities, specifically of endocrinopathies, that can actually be long-lasting and can impact quality of life. So all those discussions, as Jason alluded to, are things that patients take into account.
I’ve had the patient who says, “You know, my job is a very physical job. I need to feel in tip-top shape every day, and I don’t want to take pills that make me fatigued every day.” It’s very appropriate to go on immunotherapy. I have the patient who says, “I have a family, and I’m interested in having a pregnancy in the next few years. I wouldn’t want to affect my chances of fertility because of endocrinopathies and would prefer to take targeted therapy.”
Those discussions offer us the opportunity to personalize our management, mostly based on clinical characteristics and patient preference over, at this point, biomarkers. Because the next step really should be trying to understand whether we can actually direct those patients to a bit more science, around predictors of response, or even integrated modeling to tell us…