The Future of Precision Medicine in CSCC

Shubham Pant, MD:Once you’ve treated with these agents, are you thinking of giving them in the neoadjuvant setting? You were saying these shrink, you get a response rate and everything. So where do you think the science is going with the immune checkpoint inhibitors?

Nikhil Khushalani, MD:That’s a great question, Dr Pant. That is exactly where I think the power of a multidisciplinary team comes into play. We all know that patients who have node-positive disease in CSCC [cutaneous squamous cell carcinoma], if they undergo surgery first followed by radiation, a good percentage of them will actually do very well. But the ones that are clearly even higher risk, for example, with larger tumors greater than 2 centimeters in the nodes with evidence of extracapsular extension, these are patients that are very high risk for failure, even after surgery and radiation therapy. One has to start wondering if we bring these immune checkpoint inhibitors earlier in that process, as you mentioned, the neoadjuvant setting, so preoperatively….

At our center, we certainly discuss these within our multidisciplinary group. We have, particularly for these borderline resectable patients or cases where we feel that patients may be better served not only to try to reduce the morbidity of surgery, but also to allow the disease to declare its biology. The last thing you want is doing an extensive operation with node dissection, only to find out that the first or second scan after the operation demonstrates distant metastatic disease. So you wind back the clock and say, “Could we have done this differently?”

There are clinical trials underway or being planned to specifically test this in a neoadjuvant setting, so that a priori define a cohort of patients where you would treat them with immunotherapy. And when I say neoadjuvant, I mean a specific number, not let’s treat, let’s see what happens, and let’s treat more, and then we’ll decide. So this is to specify a number of cycles of therapy and then decide, and at that point….

Shubham Pant, MD:In 2 months, 3 months, some cutoff point.

Nikhil Khushalani, MD:Exactly. So give them a cutoff point because that also allows us to study the disease. Because with adjuvant therapy, the real power there is getting a tumor biopsy, which you have ahead of time, and then when you take them to the operating room you have more tissue as well. Now, you may end up seeing a dramatic response from a pathologic standpoint. And then to understand, if we can develop algorithms where patients, for example, who develop pathologic complete responses, do they need more postoperative therapy, or can we actually observe them?

Shubham Pant, MD:Like the breast cancer paradigm, right?

Nikhil Khushalani, MD:Exactly. I think that’s really exciting because, for the first time, we have drugs or a class of drugs and now an approved drug that patients tolerate very well. So I think it really becomes critically important to have very thoughtful decisions in designing the next generation of clinical trials with CSCC. So I’m fortunate that I’m part of that revolution. I think that we can actually see, in front of our eyes, the benefit to patients.

Shubham Pant, MD:That’s awesome. Thank you so much.

So Dr Khushalani, tell me, this has been a really interesting discussion about a rare tumor. I’ve dreamt about it myself, but still, there is so much to learn out there. There are so many things happening that I think it’s good to have this interaction so we can inform, educate those outside about the things that are happening in these rare tumors. So for somebody in the community, when these rare tumors show up, they know what is going on in the science and everything, and what the new therapies available to them are. But tell me, kind of wrapping up this whole discussion, what are some take-home points for our community oncologists who maybe are seeing this show, or even for other academic oncologists?

Nikhil Khushalani, MD:If I had to summarize and give a couple of bullet points, I think number 1 is to recognize that we now can manipulate the immune system in CSCC, or cutaneous squamous cell carcinoma. We’ve had drugs that work, but now we have drugs that work better and hopefully will work longer. Dare I use the word “cure” in these patients with locally advanced or metastatic disease? I think it’s too early to tell. Long-term follow-up from the data from these trials that have now led to the approval of cemiplimab will certainly inform us better. I would not use that term yet, but I definitely think we’ve benefitted patients.

It is important to recognize that even though these drugs are very well tolerated, the checkpoint inhibitors, anti—PD-1 [programmed cell death protein 1] inhibitors, there is potential for toxicity, and therefore should be done by individuals experienced with its use. And this could be dermato-oncologists if they’re experienced with the use of immunotherapy, certainly medical oncologists, and part of a multidisciplinary team.

I think the other take-home is to try and identify ahead of time who would be the most appropriate candidates for the use of systemic therapy in this disease. Sometimes, in the past, we would see some of these patients a little too late in the course of their disease. I would actually encourage that these patients come to the surgical oncologist, or the radiation therapist, or the medical oncologist a little bit earlier in the course of their disease, recognizing when to appropriately use this.

And, finally, these therapies are not yet for very early stage disease. So by no means does this supplant surgical resection or Mohs micrographic surgery for very early stage cutaneous squamous cell carcinoma. It certainly should be not used under that domain.

Shubham Pant, MD:It’s an exciting time for you in cutaneous squamous cell skin cancer. So best of luck for all your research endeavors and for the future of science.

Nikhil Khushalani, MD:Thank you very much. It was my pleasure being here.

Shubham Pant, MD:Thank you so much, Dr Khushalani.

Thank you, Dr Khushalani, for this insightful discussion, and thank you to our audience for watching thisTargeted Oncologypresentation on precision medicine in CSCC.

Transcript edited for clarity.