Future of BCC and CSCC Therapy

Final thoughts on unmet needs in the management of BCC and CSCC and how to approach future treatment of these diseases.

Transcript

Omid Hamid, MD: While we have made huge inroads into the therapy for locally advanced and metastatic cutaneous squamous cell carcinoma [CSCC] of the skin, and basal cell carcinoma of the skin, there still remain a lot of questions to be answered. We have high response rates in these tumors with immunotherapy. But more than 50% of the patients are not responding. The question there is, how can we improve immunotherapy to benefit these patients? Would it be a better predictive or prognostic marker? Would it be combinations that elicit a better immune response, either by priming the immune system and then boosting with a checkpoint inhibitor, or working together simultaneously?

We have the ability to utilize other types of immunotherapy for our patients. There is ongoing experimentation through clinical trials with oncolytic viral therapy, which is direct injection of immunotherapy into basal cell carcinomas and cutaneous squamous cell carcinomas of the skin, with some interesting results. We can look into other types of therapy, whether it is CAR [chimeric antigen receptor] T-cell therapy or other types of immunotherapies for our patients. Obviously, for basal cell carcinoma, the ability to combine targeted therapies with hedgehog inhibitors and immunotherapy should be looked at. As we said, there are mutations that exist in cutaneous squamous cell carcinomas that exist in head and neck squamous cell carcinomas. The ability to target those either singularly or in conjunction with immunotherapy through checkpoint inhibition is being looked at currently.

Morgana Freeman, MD: When thinking about unmet needs for basal cell carcinoma, I think 2 areas exist. The first is what to do when that patient is intolerant of a hedgehog inhibitor or when that patient progresses on a hedgehog inhibitor. This is because, right now, there are a lot of unanswered questions. As I mentioned, these questions revolve around what the next line of therapy should be. Is immunotherapy appropriate or is EGFR inhibition appropriate, for example? That latter question can probably be answered by more mass next-generation sequencing to see what other markers or what other genes might be playing a role in that particular patient population. The other thing to keep in mind is what to do for those rare patients with Gorlin syndrome because they oftentimes will exhaust the hedgehog inhibitor pathway early.

With CSCC, there’s a whole basket of unanswered questions, primarily what to do for the very vulnerable solid organ and bone marrow transplant population. We know that by exposing those patients to immunotherapy, we’ve put them at risk of graft rejection, and don’t know if there’s a subset in the transplant patient population, for example, where it might still be safe to do it. So a question would be, what are the safety and efficacy implications for patients who are immunocompromised because of prior transplant history? Similarly, what are the safety and efficacy implications for patients with a history of CLL [chronic lymphocytic leukemia] or HIV? That’s another patient population where there’s a lot of CSCC that’s seen. Thirdly, with CSCC, when thinking about those patients for whom immunotherapy is appropriate, what do we do when they progress on PD-1 [programmed cell death protein 1]? I’m borrowing some of these questions from what we know about melanoma. But we learned that with melanoma, by combining CTLA-4 [cytotoxic T-lymphocyte—associated protein 4] with PD-1, we could significantly augment the clinical impact of those drugs. CTLA-4 is being looked at in combination. Is there a use for radiation plus cemiplimab or PD-1 therapy? Is there a role of intralesional therapy? Can we use that as a way to activate the immune system and combine that with PD-1 backbone? Those are all actually very exciting research questions that are being answered now in clinical trials, so stay tuned.

As a specialist in skin cancer who sees these cases every day, my advice to the listening oncologist would be to engage with your team members early. Talk to your dermatologist, talk to your referring surgeons, talk to your radiation oncologist, and have intelligent multidisciplinary discussions around what the impact of your therapy is and might be for that particular patient. We know that these drugs work well. We know that these drugs work fast, and oftentimes to avoid the patient coming to you too late, get involved early in the discussion and advocate for the power of your therapy. That is absolutely something that I would say, and I would encourage everyone listening to this interview to do, because ultimately, we all want to achieve the same goal for our patients.