In this interview, Dr Aaron Farberg explored key factors in identifying suitable candidates, molecular markers' role, multidisciplinary approaches, current systemic therapy options, recent clinical trial findings, co-management challenges, and emerging immunotherapy developments in advanced basal cell carcinoma (aBCC) and cutaneous squamous cell carcinoma (aCSCC).

Aaron S. Farberg, MD, is a board-certified dermatologist and Mohs surgeon specializing in skin cancer and cosmetic dermatology. Dr Farberg is also the lead editor for a book on technology in skin cancer and has been a clinical investigator in many studies with some being FDA clinical trials.

Transcript:

Can you discuss the key clinical and pathological factors that help in identifying patients with advanced cutaneous squamous cell carcinoma (aCSCC) and advanced basal cell carcinoma (aBCC) who may be appropriate candidates for systemic therapy?

Dr Farberg: So, how do you identify advanced cutaneous squamous cell or locally advanced basal cell carcinoma? Well, there's a number of different clinical and pathologic features that we all know lead to us believing that one of these lesions is going to be high risk. These are often included in various staging and guidelines. Think of the NCCN or Brigham and Women's A JCC, but oftentimes it's our own clinical gestalt and understanding of what a complex lesion is, what is a complex cancer in one of these patients, but they do harken back to, uh, simply these clinical pathologic features and the squamous cell side of things. They might be a little obvious, but they really are high risk features. Is it big? Does it include perineural invasion? Does it go down to the fat or does it include the bone?

If you think about the histopathology side of things, is it poorly differentiated? But it's also good to think beyond just these clinical pathologic features, particularly for basal cell. You have to think about the patient. Is it a large lesion in an area where perhaps, you know, a surgery would leave a lot of morbidity, or is it a patient that's much older and maybe isn't a good surgical candidate, or is it a, a lesion on a patient where they've had so many surgeries and they're done with surgery and they don't want to see the moose surgeon anymore? These can also be advanced skin cancers that may benefit from systemic treatments.

What role do molecular markers or genetic profiling play in determining the eligibility of patients for systemic therapy in aCSCC and aBCC?

Dr Farberg: We are currently utilizing a list of clinical and pathologic features to best identify which cutaneous squamous cell and even locally advanced basal cells are high risk. And although we have good systems now, we're always striving to do better. And one of the best markers out there currently is the molecular testing, particularly the 40 GEP tests, which helps us stratify or really identify patients with cutaneous squamous cell that are either lower risk or actually are at higher risk, or even very high risk at where we can then find risk aligned treatment.

In the context of advanced CSCC and BCC, how do you integrate a multidisciplinary approach into the management plan? What are the collaborative efforts involving dermatologists, oncologists, surgeons, and other specialists?

Dr Farberg: When it comes to advanced cutaneous squamous cell or basal cell a multifaceted approach and a multidisciplinary approach is absolutely critical. Dermatologists, I'm always stressing this to my colleagues, even though you may not do the surgery or the radiation or provide the immunotherapy, you are often the gatekeeper to these procedures and who you refer to which physicians you refer these patients to, is often the treatment that they're going to follow. Remember, you are often the diagnosing physician, and so patients are seeing you first and trusting you the most. And so where and who you guide them to will truly matter.

Could you provide an overview of the current landscape of systemic therapy options for advanced CSCC and BCC, particularly focusing on immunotherapeutic agents?

Dr Farberg: When you get to advanced cutaneous squamous cell treatments become much more limited, particularly when it comes to immunotherapy. We have a wonderful drug that can help us in these sorts of situations. It's called libtayo, also known as cemiplimab. It's been shown to perform quite well for these patients with, advanced squamous cell diagnoses. On the basal cell side of things, we also have cemiplimab but we also have these hedgehog inhibitors as well. It's really important that we have these options for these patients because as I mentioned previously, not every one of these patients is a candidate for surgery. And we really have to think about these patients as a whole. You have to think about their quality of life and what they’re really the goal is for the treatment of these patients. And when you think about, for example, immunotherapy and cemiplimab, you recognize that the, the efficacy for this drug in these very, very complex patients is actually quite good with low to minimal adverse events, at least ones that we can all manage.

What are the key findings from recent clinical trials regarding the efficacy and safety of systemic therapies, and how do these findings impact your treatment decisions in clinical practice?

Dr Farberg: At the winter clinical 2024 Dermatology Conference in Honolulu, gave a lecture highlighting the use of cemiplimab. And really one of the core points of that talk was highlighting the safety in, in relation to the efficacy of that immunotherapy. We know it works, but of course, as dermatologists we're worried about any adverse events and side effects. And as we went through the safety slides as well as the adverse event profile, you recognize that far and few patients actually discontinued the medication, which leads us to understand that wow, it was actually one that most of these patients wanted to stay on because A, it was working well, but B, they were able to tolerate any of their adverse events.

What challenges do you encounter in the co-management of patients with advanced CSCC and BCC, and how do you navigate these challenges in clinical practice?

Dr Farberg: The challenges in co-managing these patients with advanced non-melanoma skin cancer is working together with our colleagues. This is extra work. Of course, it would be much easier to simply write on the referral and send them off to the surgical oncologist or the radiation oncologist and, and let the patient go off and not have to worry about them thereafter. But we know that's not what we do. We then call up the, the team, the surgical oncologist or the radiation oncologist. We're discussing the case. We're taking that extra step to really work with the patient and the clinician team for this multidisciplinary approach.

Looking ahead, what emerging developments or ongoing research in immunotherapy for aCSCC and aBCC are you most excited about, and how might they shape the future of patient care?

Dr Farberg: The exciting advancements with immunotherapy for non-melanoma skin cancer would be in regards particular its utilization in a neoadjuvant way. Oftentimes with treating these patients, again, I have to stress what is the goal of their care, and many times we can utilize systemic therapy simply to shrink the tumor down, which makes the surgery or the definitive procedure a whole lot easier. This is utilized both on the immunotherapy side as well as the hedgehog inhibitor side as well. Also on the horizon is gene expression profiling molecular testing. Really identifying and stratifying these patients into various risk categories helps us understand who could benefit from an immunotherapy, who could benefit from radiation, and importantly then who can forego these types of treatment or this intensive level of surveillance.