Jennifer A. Stein, MD, PhD, discusses the skin-related adverse events for patients on treatment for melanoma, as well as the importance of identifying new primary melanomas.
Jennifer A. Stein, MD, PhD
Being on treatment for melanoma still requires physicians to examine their patients for new primary melanomas, which are likely to occur especially in patients on a BRAF inhibitor, according to Jennifer A. Stein, MD, PhD.
Moreover, the skin-related adverse events (AEs) patients experience, regardless of their treatment with a checkpoint inhibitor or with a targeted therapy, also need to be closely monitored and, if necessary, properly managed with topical steroids or antihistamines.
In an interview during the 2017 OncLive® State of the Science SummitTM on Melanoma and Immuno-Oncology, Stein, an associate professor of dermatology at New York University School of Medicine in New York, discusses the skin-related AEs for patients on treatment for melanoma, as well as the importance of identifying new primary melanomas.Stein: I talked about some of the skin-related AEs with systemic treatment for melanoma, and how to look for new primary melanomas, even in patients who are already on treatment for melanoma. Patients can get AEs with immunotherapies such as ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda), and there is a set of AEs they can get with the BRAF inhibitors.
With immunotherapy—those checkpoint inhibitors—the most common AE for all organs is rash, and it is actually 1 of the first side effects that pops up in the first weeks to months. Fortunately, most of the time it’s pretty mild, and it can usually be treated just with topical steroids or oral antihistamines. Very rarely, you can have more severe AEs. I spoke about a patient who had bullous pemphigoid or, more severe sometimes, you can get Stevens-Johnson syndrome or toxic epidermal necrolysis.There are severe allergic reactions in which the skin starts to blister and actually peel off. Those can even be life-threatening but, fortunately, they are pretty rare. For the most part, people can get a pretty mild rash that is well controlled, often with just topical creams. One thing that’s really important to tell patients about the BRAF inhibitors, and with vemurafenib (Zelboraf) in particular, is that it is extremely photosensitizing—people can get this terrible phototoxic reaction. They become so sensitive to the sun that their skin blisters, so you need to make sure these patients are practicing really good sun protection while they are on vemurafenib. With the BRAF inhibitors, patients can get new skin cancers, especially squamous cell carcinomas. They sometimes get a subtype of squamous cell carcinomas called keratoacanthomas. They are not very aggressive squamous cells; they grow quickly and can sometimes go away completely on their own. You never know which ones are going to, though, so normally we just scrape them off and make sure they’re completely gone.
We usually see this in patients in whom you generally would expect to see squamous cell carcinomas, so that would be older patients; people with light skin; people who have had a lot of sun exposure; and especially patients who had squamous cell carcinomas before they went on the drug.
One other thing to make sure to look for in patients who are on a BRAF inhibitor is that they are not getting another new primary melanoma. When I first started seeing patients on BRAF inhibitors, I didn’t realize how important it was. You would think patients are taking a medication to treat melanoma [so how could they get another one?] But, in fact, there is literature that makes it clear that you can get new primary melanomas [while on treatment]; it is something we have seen. It can be anywhere. Patients who have had 1 melanoma in general are at higher risk for having a second melanoma, and the interesting thing about the new melanomas that patients get while they are on a BRAF inhibitor is that the new melanoma tends to be BRAF wild-type, which makes sense because patients are on a drug that treats the BRAF-mutant melanoma. If the patient is having a mild skin AE, that is [normally] a mild rash that involves less than 30% of the body surface area. Usually, you can give them a mid-potency topical steroid—something like triamcinolone alone is a good thing to start with.
Also, some patients are just itchy without many skin findings and these patients can also benefit from a topical steroid, but also oral antihistamines are good for the itch, too. During midday, you want to give them something not sedating and then, at night, giving something sedating is helpful because when people are itchy it keeps them from sleeping. Therefore, something sedating helps the itch and lets them get a good night’s sleep. We know that patients on a BRAF inhibitor can get new skin cancers, but patients on a combination of BRAF/MEK inhibitors actually get fewer new squamous cell carcinomas.
We think the reason that patients on BRAF inhibitors get new squamous cell carcinomas is that in the keratin ascites, the other skin cells themselves, there is an activating RAS mutation. The MEK inhibitor helps with that. It is very important to check for new primaries. That’s why we know to check patients on a regular basis; if they get a second melanoma, it tends to be found nice and early.
We [dermatologists] do total body skin exams, and oncologists can do them, too, but sometimes it’s helpful for an oncologist to partner with a dermatologist. For example, a lot of my patients will see the oncologist and see me, and we spread out the visits so they are getting 2 sets of eyes.
Some melanoma patients aren’t “moley” at all. They might have just gotten 1 bad melanoma and have not much else on their skin. For those patients, it’s easy to do their skin checks. But then, there are the patients with a history of melanoma who have tons of moles. Lots of them have atypical moles where each mole looks a little bit like a melanoma. That is really challenging, because it is like camouflage—you have to find the actual melanoma, [if it’s there,] when everything looks a little bit funny.
The first step when you are looking at somebody “moley,” is to take a step back and think, “What is normal for this person in front of me?” Light-skinned people make light moles, darker people make darker moles, some people have moles with a little raised center, and other moles are flat. Once you figure what that normal signature mole pattern is, that will clue your eye in to when you see the “ugly duckling”—the one that doesn’t fit in with the rest of the mole patterns.
If you see something that looks like it doesn’t fit in, that is when you want to take a closer look. We use a technique called dermoscopy, which is just a handheld lighted magnifier that changes the optics of the surface of the skin and gives you a deeper look under the surface of the skin. You can see certain colors and patterns that help you find a subtle melanoma, and it also helps you to reassure you of a mole that’s harmless and it saves unnecessary biopsies. It has been around for a number of decades, but it has become much more popular in this country within the last decade or so.
We also do a lot of imaging, so for people who have lots of moles, sometimes we will do total body topography, where we take pictures of the entire surface of their skin. That helps us notice if there is something that is new or changing, because change is so important in finding new melanomas.
The last important thing to educate patients about is doing their own skin self-exams. If patients find a melanoma at home, they tend to find it earlier than if they were to wait until they get to the doctor’s office to have it found. We also tell patients to have a partner help them examine their skin. There are a bunch of papers that have been written about partner-assisted skin exams. For example, wives are very good at finding melanomas on their husbands’ backs because the back is the most common spot for melanoma in men. It is hard to see your own back. In fact, the better the relationship is between the partners, the better they are at finding the new melanomas.
If you live alone, you can use mirrors. But even better than mirrors is using your cell phone camera. Fortunately, the cameras on cell phones have gotten so good that you can really get a good picture of your back. We wrote a paper last year to use a selfie stick—we call it the “skin selfie exam.” You could also get a friend to take a picture of your back. The benefit of having that picture on your camera is, then, you can zoom in on it and you have a record so you can watch going forward to see if there is any change.