Systemic Treatment of CSCC

Experts discuss the primary goals of therapy for nonsurgical candidates and the impact of immunotherapy for patients with advanced or metastatic CSCC.


Omid Hamid, MD: The primary goal for patients with locally advanced or metastatic cutaneous squamous cell carcinoma [CSCC] is the ability to control the disease, to prevent progression, and of course, prevent significant morbidity from the lesion. At the current time we have a therapy that has a high response rate, a durable response rate. For certain patients, it can be utilized in the multiply recurrent setting, as a neoadjuvant therapeutic, or as a therapy to control life-threatening metastatic disease.

Morgana Freeman, MD: When thinking about the primary goals in the discussion that I have with patients and how that should be generated by the medical oncologist, patient preferences are absolutely critical. This is a disease that unfortunately can be very disfiguring. By the time patients have come to see me, they’ve been through multiple surgeries and have suffered some of the ill effects of the cosmetic outcomes perhaps of repeated surgical excisions and possibly even radiation. That’s definitely something to consider, and balance that against their quality of life desires.

Many patients, for example, don’t want to go through radiation treatment again because of claustrophobia or because of toxicities that they may have experienced. The other thing to keep in mind if we’re talking about metastatic disease, meaning to distant organs, again is quality of life and what the patient’s expectations might be for treatment balanced against the adverse effect profile. We’re very fortunate that we live in an era of immunotherapy now, so that conversation is a lot easier to have. But before when we didn’t have immunotherapy, chemotherapy and targeted receptor-based therapy would sometimes be an unwelcome conversation between patients and families, especially when thinking about what their limited prognosis might be.

Omid Hamid, MD: Unfortunately, my past experience with chemotherapy, radiation therapy, and also targeted therapies for cutaneous squamous cell carcinoma that has been locally advanced or metastatic, has been poor. The literature has shown that response rates are low, there is toxicity with therapy—risk of neutropenia and infection with chemotherapy, and adverse effects with targeted therapy. All of that would be worthwhile if we had a high response rate, or at least a high duration of response. We hadn’t seen that previously with chemotherapy or targeted therapies.

Unfortunately, patients who have multiply recurrent locally advanced disease in the cutaneous squamous cell carcinoma setting have had radiation and therefore, there is an inability to utilize reirradiation at appropriate doses without the risk of significant morbidity.

The impact of the introduction of immunotherapy for cutaneous squamous cell carcinoma that’s locally advanced and metastatic has been huge. First, I’d like to point out that this is a therapy that’s also indicated for patients who have multiply recurrent therapy that’s not amenable to reirradiation or surgery. That is, for these patients who have recurrent disease where surgery has failed, and radiation has failed. You can utilize this for disease control.

What we found is that not only is this therapy very tolerable with a low incidence of toxicity, but it also has a high response rate. Response rates for locally advanced and metastatic disease go at about 46% to 48%. For the duration of response for these patients, 6 months or greater is greater than 60%. We have seen patients who have failed all modalities including surgery, radiation, and chemotherapy be able to have a meaningful benefit—not just response, but disease control above 60% to 70%—that allows them to continue without the severe morbidity of treatment and the severe morbidity of disease. Also, it more than likely makes a dent in the mortality of this disease.

Morgana Freeman, MD: I feel very fortunate to be practicing in an era of immunotherapy with this cancer in particular. The advent of cemiplimab in this day and age has proven tremendous benefit for patients. When we consider the response rates that we’re seeing in the 2 trials that led up to the drug approval, when we saw the ongoing responses that were captured using immunotherapy compared to what we see with chemotherapy or targeted therapy, and then when we also saw very favorable tolerability profile, it completely changed the game. It also changed the conversation to be had with patients when talking about expectations for disease management. I feel that we’ve seen some tremendous outcomes with cemiplimab, and hopefully we’ll continue to see them as the drug is used more and more.

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