Anisha Patel, M.D.  Hi, I'm Anisha Patel. I'm an associate professor of Dermatology at MD Anderson Cancer Center, and I'm here with Dr. Christine Parseghian, also an associate professor of Gastrointestinal Medical Oncology at MD Anderson, and this is the Cancerwise Podcast. Thanks for joining me today. We are here to talk about EGFR inhibitors or epidermal growth factor receptor inhibitors and the skin toxicities that can force patients to pause or stop their cancer therapy. Can you tell us a little bit about how EGFR inhibitors are used in colorectal cancer? 

Christine Parseghian, M.D. Of course, and thank you, Dr. Patel, for having me. It's great to see you again. So anti-EGFR, basically epidermal growth factor receptor inhibitors, otherwise known as anti-EGFR inhibitors, are a targeted therapy. They're used for several cancer types, particularly certain types of colon cancer. The EGFR inhibitors target certain growth receptors that facilitate kind of tumor growth in patients with colon cancer who lack a mutation in the RAS gene. They are highly effective and a crucial part in treatment for these patients. But unfortunately, about 80% of these patients ultimately will develop, as you know, some degree of skin toxicity. And this can affect, obviously, treatment outcomes, will require dose reductions, and even treatment discontinuation in some patients. So, it's not something to be taken lightly. So, actually, Dr. Patel, I think this raises a good point. Can you tell us a little bit about what you see in terms of the acne rashes that develop in these patients and how to best address them? 

Anisha Patel, M.D. That's a great point, and we've been working together for many years and have taken care of many patients together. And I think we're both really familiar with this being the most common skin toxicity for EGFR inhibitor-treated patients and the same receptor that's on the cancer is also in the skin so when we see the blockade and the tumor we're also seeing the blockade in the skin which is why we have such a high incidence of rash. And we call it acneiform because it mimics acne. So, it looks like teenage acne that you would see with, like, sort of those deep cysts and inflammatory papules and pustules. But the mechanism is different and it's caused directly by that EGFR inhibition. And usually you still see it in the normal acne distribution on the head and neck. You can see it on the chest and the upper back. It can be pretty itchy or painful for patients who have those deeper, like cystic or nodular lesions. And the thing that is, I guess, most impactful to patients is their ability to stay on their cancer treatment. So, their ability to stay the treatment that you are prescribing for them when they have this rash, particularly when it's very severe. So, from the Dermatology standpoint, it's our goal to manage the rash in a way that patients are able to stay on the cancer therapy that you think is best for them. And can you explain to us a little bit how you think skin toxicities affect sort of patient outcomes and their tumor response? 

Christine Parseghian, M.D. So, interestingly, rash actually is a good sign, in a sense, because it actually tells us that the treatment is working. But unfortunately, as you describe, we have several clinical trials. I mean, anti-EGFR inhibitors are also standard of care, but at MD Anderson, we have several trials with novel agents in kind of combination with these drugs. And these are often met with significant skin toxicities associated with EGFR inhibitors. So, we are having to dose-reduce therapy. Unfortunately, at times, if the skin toxicity is so bad, we have to discontinue therapy. And particularly if patients are, you know, later line with minimal options, if we have to take them off clinical trial for these, it's, you know, a significant change and a significant impact on their lives. So, definitely not something to be taken lightly. I think this is where you come in a little bit. I think we, we've worked together a long time, and I think you've helped me get my patients into Dermatology and helped them through these difficult times. But I think that you have some exciting news to share a little bit about, kind of, a new way that we can approach this rash with BRAF inhibitors to prevent and mitigate some of these skin toxicities. 

Anisha Patel, M.D. In the dermatology space, we were really excited to be part of this trial. And like you said, it used BRAF inhibition, which is another signaling molecule in the same pathway as EGFR inhibition to sort of take advantage of a molecular anomaly. And the trial enrolled 117 patients. And we were able to sort of show both clinical efficacy as well as safety in our patients. It was really fun to be able to administer this trial and see how well patients did. And I think it was sort of a positive reinforcement loop for both of our departments to get patients involved with this trial. It was a wonderful opportunity. And it not only decreased the symptoms and the inflammation that we would see in our patients, but also helped the visible rash, which was really encouraging to see. And I think this was a good example of how oncology and Dermatology works together. How do you see us working together and managing these side effects? 

Christine Parseghian, M.D. Yeah, I mean, I think the key is early collaboration, right? You and I are always talking, because specifically, we have similar interests. I give a lot of anti-EGFR. I lead a lot the anti-EGFR clinical trials, and of course, this is a great area of interest for you. So, I think as we have worked together, I think that has just shown early collaboration is very important. Watching these skin toxicities closely from the very beginning, applying, kind of, supportive measures, really to keep patients on their cancer, kind of, treatment track. Because as we know, this can really affect their chemo, their outcomes, their survival. Needing to dose reduce and discontinue therapy is, you know, a significant issue that hopefully is preventable with your help and this great. New study. 

Anisha Patel, M.D. I totally agree and I think we have tried to stay ahead especially for our patients in the education and management and our groups working very closely together. This does address sort of a crucial need and advanced management for our patients especially with a low side effect profile. Our goal is always to keep people on the appropriate cancer therapy at the appropriate dosing and to avoid any unnecessary treatment delays. 

Christine Parseghian, M.D. What kinds of things are you doing, kind of as supportive measures, when I send my patients to you, what kind of things are you, are you offering them? 

Anisha Patel, M.D. I think a key thing for our patients is knowing that we're on the same team, that you and I talk to each other and that all of us have the same goal of them staying on the most effective cancer therapy and that I'm not going to give them anything that's unsafe or that you wouldn't approve of, and then really just walking them through our management algorithm and being able to do this trial gave us a golden arrow of sorts of having another novel, safe option to be able to offer. I know you have a number of patients in particular who were able to participate. 

Christine Parseghian, M.D. Can you actually tell us a little bit about how patients can be proactive in preventing some of these skin toxicities? 

Anisha Patel, M.D. That's a great question and it's one that we've had so many times that we've actually made handouts for our patients to be able to access themselves in addition to, obviously in the appointments we go over it. And so really, I think what we're seeing with EGFR inhibition is a breakdown of the normal skin barrier and that skin barrier extends down around hair follicles which is why you end up with particular rash around the hair follicles and that inflammation. So, we really encourage using bland emollients. So, using creams in particular. There is a difference between like creams and lotions, and so, creams are the thicker emollients and that's what we prefer that patients use to keep their skin hydrated and their skin barrier intact. And then also staying away from over-the-counter acne treatments. So, a lot of those are drying to the skin, have an alcohol base and can make your irritated skin even more inflamed. I think those are two big things that we have on our patient handout. And then we've worked together to make algorithms for preventative management where a lot of our patients, and I think this is something that we do really well, when you prescribe their cancer therapy regimen, you're also prescribing preventative therapies for their rash. And that helps keep people with low-grade rashes and hopefully keep them on their therapy at the correct dose. If that rash escalates, then that's when they come to us and we'll try to escalate their therapy using like oral treatments. But really preventative moisturization, and then the rash can be sun sensitive. So, educating patients on staying out of the sun, using UV protection, SPF 30 or above, mineral sunscreens, sun protective clothing, all of those can be very helpful. 

Christine Parseghian, M.D. Perfect. Thank you. And I think it's really important, as you say, a lot of patients will just become very desperate and head to the local pharmacy and get, you know, the acne treatments and the washes and the cleansers. But really important to kind of stick to the, your recommendations as you said. We've seen a lot these toxicities get worse without following these directions and Dr. Patel and her colleagues have really developed a nice algorithm, like she said, to kind of prevent some of these hopefully and mitigate them. 

Anisha Patel, M.D. And as more treatments come up, we're seeing this as your group does more and more clinical trials, that early management of these rashes becomes more critical to keep people on their most effective therapy. 

Christine Parseghian, M.D. Especially when it comes to clinical trials. We really try to keep patients on. So, ideally, sooner the better. Unfortunately, a lot of clinical trials will only allow a certain degree of toxicity before having the patient come off. So, really, I send my patients to Dr. Patel very early on in the course, and she's always happy to help so that we can hopefully again, prevent a toxicity that would require a patient to be discontinued from a otherwise, you know, life-extending, life-saving trial. 

Anisha Patel, M.D. And I think that was one of the fun parts about this trial, is that it's not a primary cancer trial or a primary tumor trial. It's a trial to treat the side effects of cancer therapy, which there's not a lot of trials in this space or a lot of companies that are even making drugs that focus on this. So, it was really fun to be able to participate in this new space and even be able to offer this to our patients at MD Anderson. I think we have a really motivated group of patients here and being able to enroll them and offer this new therapy was really fun in this space that hasn't previously been given much attention. 

Christine Parseghian, M.D. I think it's really exciting. I'm gonna go a long way, and I think I'm a little bit biased, obviously, in the colon cancer kind of era, but this will be very important in all tumor types. 

Anisha Patel, M.D. Thank you so much for being here today, Dr. Parseguin. This was a great conversation. 

Christine Parseghian, M.D. Thanks so much for having me. It's always a pleasure to see you, Dr. Patel. 

Anisha Patel, M.D. For more information or to request an appointment at MD Anderson, call 1-877-632-6789 or visit MDAnderson.org. And thanks for listening to the Cancerwise Podcast from MD Anderson Cancer Center.