Targeted Therapies in Advanced Cutaneous Squamous Cell Carcinoma - Episode 4

Treatment Options in CSCC

January 17, 2019

Shubham Pant, MD:So when a patient comes to you, what is the primary treatment for these cancers? What if the patient comes to you with nodal or advanced disease? What is the primary treatment? You said something with radiation. What is the primary treatment that you use for this cancer?

Nikhil Khushalani, MD:So this has really evolved over time.

Shubham Pant, MD:Well, let me say 6 months back. What would you use?

Nikhil Khushalani, MD:So 6 months back. So again, I’m biased. Obviously, Moffitt Cancer Center is a clinical center, so we have had access to clinical trials. But you know talking very generally, when patients present, this is still primarily a surgical disease, at least in the onset, even with patients who have node-positive disease. As long as a good multidisciplinary team can evaluate that patient who has palpable nodes—so macroscopic nodes, as we would describe them—and determine their eligibility or noneligibility for surgery. I think that’s…sort of the fork on the road. If they are eligible for surgery and staging, typically CT [computed tomography] imaging demonstrates no evidence of distant metastatic disease beyond the confines of the surgical basins. Then typically those patients, as long as the surgery is not considered to be unusually morbid or cosmetically disfiguring, particularly on the head and neck area—we see a lot of patients with scalp CSCCs again, primarily related to sun exposure. As long as the surgery can be adequately performed with negative margins with good recovery, that tends to be our first treatment of choice.

In selected patients, particularly those that are considered high-risk for recurrence—and again, a variety of criteria to define that from a nodal perspective, including the size of the nodes, the number of the nodes, and the presence or absence of a characteristic called extracapsular extension, the presence of EC, or extracapsular extension, puts these patients at a higher risk for regional recurrence—we would consider those patients for adjuvant radiotherapy.

Shubham Pant, MD:And the radiation after all has been...

Nikhil Khushalani, MD:The radiation after the surgery to reduce a risk of local regional recurrence. The key question in that which was recently answered was: Does the addition of chemotherapy to radiation improve the odds of cure or reduce the risk of regional relapse? The TROG, which is the Trans Tasman Radiation Oncology Group, conducted a very well-designed randomized trial recently that was reported earlier this year, in which they randomized patients with high-risk cutaneous squamous cell carcinoma and nodal involvement to receive postoperative radiation versus postoperative radiation, standard dosing, plus weekly carboplatin. And essentially what they found was that there was no benefit to the addition of chemotherapy.

There are some caveats there, however. These are patients who even in the control arm actually did better than anticipated. So the question is, can we still further truly dissect down that data to identify who is truly at even a higher risk, that may warrant chemotherapy in addition to radiation? We’re still trying to understand that.

Shubham Pant, MD:But right now the standard of care would be radiation?

Nikhil Khushalani, MD:Postoperative radiation.

Shubham Pant, MD:Now suppose somebody presented with a lesion that is not surgically resectable. What would the first treatment be?

Nikhil Khushalani, MD:So there, again, we have a variety of options. And traditionally for those patients we would have considered either definitive radiotherapy by itself, a combination of chemotherapy plus radiotherapy, and now more recently—based on data and our better understanding of the biology of this disease—definitely…immunotherapy for them. And this is immunotherapy targeting the PD-1, or programmed cell death protein-1, pathway.

We now actually have a drug that’s the first of its kind to be approved in CSCC, which is cemiplimab, which is a human antibody against PD-1. Just received approval a couple of months ago based on some very good, albeit early data, but very good data that we actually participated in that clinical trial as well.

So I think the options have certainly expanded. One of the caveats to recognize in these patients who present, because this is a disease that tends to increase in incidence with age, is that these are patients who may have associated comorbidities. They may have renal failure, or at least a decline in the GFR [glomerular filtration rate]. So it’s harder to get in drugs such as platinum, which tend to be used more commonly.

Shubham Pant, MD:A cisplatin and drugs that can cause issues.

Nikhil Khushalani, MD:Nephrotoxicity, correct. So it’s a little bit harder to get those drugs into these patients. The traditional drugs that we use would be platinum agents, taxanes, including paclitaxel, 5-fluouricil. Very similar to what we would do with head and neck mucosal squamous cell carcinoma. And then we also have drugs that are targeting the epidermal growth factor receptor pathway, EGFR. Typically, cetuximab or panitumumab. Again, these responses to chemotherapy tend to be modest, or even to targeted therapy tend to be modest. We see a small percentage of patients developing complete responses as well. But the duration of response tends not to be as durable.

Shubham Pant, MD:So when you do the therapy, chemotherapy, or maybe you can control it for some time, but it’s not durable, and that’s where newer therapies are coming into play.

Nikhil Khushalani, MD:Exactly.

Shubham Pant, MD:Newer clinical trials and new approvals coming into play.

Nikhil Khushalani, MD:Exactly.

Shubham Pant, MD:You can talk more about that in our next segment.

Transcript edited for clarity.