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Migden Reviews Updated Data for PD-1 Agents in Case Review of cSCC

Tony Berberabe, MPH
Published Online:6:52 PM, Fri September 20, 2019
Michael R. Migden, MD
Michael R. Migden, MD
Michael R. Migden, MD, spoke with a group of physicians during a Targeted Oncology live case-based peer perspectives discussion about responses in patients with cutaneous squamous cell carcinoma (cSCC) to immunotherapy treatment. Migden, an associate professor in the Departments of Dermatology and Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, reviewed the treatment options and potential responses based on a case scenario of a patient with cSCC.

An otherwise healthy, single, 69-year-old, fair-skinned man presented to his primary care physician with what he described as a wound behind his ear that was not healing; he reported first noticing it at least 4 months earlier and complained of recent onset of numbness in the area. He was a retired construction worker. He had an ECOG performance status of 1. 

The visible ulcerated lesion was 4.5 cm in diameter and >5 mm deep. There were no palpable nodes. A biopsy confirmed a poorly differentiated, infiltrative, postauricular cSCC lesion with 7-mm invasion into subcutaneous fat. 

TARGETED ONCOLOGY: What additional testing would you order to aid treatment planning for this patient?

Migden: I would order a CT of the area, including the neck. We would want to make sure both the carotid [artery] and neck are clear.

TARGETED ONCOLOGY: What are some of the high-risk features of this patient with cSCC?

Migden: Size is a factor. In this patient, we need to be aware of the >2-cm [diameter] along with the 7-mm depth with invasion into the subcutaneous fat. The numbness is also concerning, as are the poorly differentiated [borders].

TARGETED ONCOLOGY: How do you define locally advanced cSCC?

Migden: I am one of the proponents who say we do not want to make it too narrow because it could exclude patients. Locally advanced cSCC is a nuanced, multifaceted presentation. It can occur in a wide range of presentations. There are many patient-specific diagnosis and treatment considerations, one of which is surgical aversion or surgical fatigue. For example, I had a patient who told me, “I’d rather die than have another major surgery.” He had undergone many big surgeries and did not want to go through another one.

So I’m not one of these people who are in favor of saying, “Well, if the surgery can technically be done, then all I can offer you is surgery.” I’m not one who can make that judgment.

I’m more in favor of saying that locally advanced disease is defined as a patient who is not a good candidate for surgery for a variety of reasons, has failed prior surgeries, is not a good candidate for radiation, failed prior radiation, or is unable to take more because of the total dose. That is the kind of defini­tion that is more broad and that allows for these patient-specific considerations.

You should always have a multidisciplinary discussion with a tumor board if possible. If not, maybe call a colleague, or call a head and neck surgeon if you are a medical oncologist. If you are a dermatology oncologist, call a medical oncologist. Even if it is not a formal board, just call to have the discussion: “This is what I have. What do you think?”

From there, go to the patient and say, “These are the recom­mendations from my colleague and me.” If the patient gives a lot of pushback and decides not to follow your advice, you have to think about looking at options besides the aggressive ones.

People want to put “locally advanced” in a box. I am not a proponent of that because I do not want to harm any patients by telling them that they don’t meet the criteria. If I had to sum up what locally advanced is, I’d say it involves multiple surger­ies failing or patients who are not good surgical candidates for a variety of reasons: either the tumor cannot be removed in its entirety because of its large size, or the tumor could be removed, but the removal will result in significant disfigurement or dysfunction.

TARGETED ONCOLOGY: How do you define metastatic disease?

Migden: Most folks know this: It is either local regional [lymph] node metastases, or it is distant metastases, which often end up in the lungs or bone.

It is interesting because I was looking at the enrollment criteria for CARSKIN [NCT02883556] and KEYNOTE-629 [NCT03284424], but [patients on these trials] had a lot of distant metastases. My understanding is that about 20% of the cases involve distant metastases compared with local regional disease. If you look at the morbidity and mortality, the locally advanced and the local regional disease have substantial morbidity and mortality. It is the lion’s share of the problem.

TARGETED ONCOLOGY: What about the cosmetic effects of the surgery?

Migden: I was the principal investigator on the phase II registration trial for cemiplimab [Libtayo], and I helped develop some of the criteria. One of the criteria for locally advanced disease would be [that it was] technically possible for surgery but could result in severe dysfunc­tion or deformity. I was specific that this needed to be included. This would include loss of most or all of a facial appendage, and an auric­ulectomy was one of the things that could qualify.1

TARGETED ONCOLOGY: What type of responses to cemiplimab can be expected? Is there a way to determine who is going to have a good response to cemiplimab?

Migden: We have seen response rates in the 45% to 50% range.1

That is a hot topic these days because there is a lot of discus­sion about biomarkers, and it is an active area of investigation. The things that people talk about are PD-L1 expression and tumor mutational burden [TMB]. Unfortunately, there are many types of PD-L1 analysis. There is analysis in the tumor itself and analysis within the immune cells that have infiltrated the tumor, and you could get potentially different results. There are also different anti­bodies, like 22C3 from the autostainer Dako [North America, Inc] and others.2 These use IHC [immunohistochemistry], where they process the tumor. The pathologist is visually [inspecting] what percentage of the total tumor has this label that lights up.

PD-L1 does not always track with response. In some cancers, [PD-L1] may track, but in cSCC, it does not appear to be a great correlation. Actually, there is not much correlation, whereas TMB looks promising based on early exploratory analysis. TILs [tumor-infiltrating lymphocytes] are another option undergoing research, as are neoantigens. These are things that are, hopefully, coming.

TARGETED ONCOLOGY: What do the guidelines say about cemiplimab?

Migden: The guidelines do not include it as a systemic therapy option yet, [but it is cited as a consideration for patients with advanced or metastatic disease who are not candidates for curative radiation or surgery].3 But I expect that to change because it is approved by the FDA.

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