Skin Cancer - Episode 7

Case 3: Recurrent Metastatic cSCC

November 25, 2019

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Ahmad Tarhini, MD, PhD:The next case is a recurrent metastatic cutaneous squamous cell carcinoma case. This is an 82-year-old man from Florida with a history of multiple resections of squamous cell carcinoma on the neck, back, and shoulders who presented with a new preauricular lesion. The biopsy revealed a deep lesion, more than 7 mm, that exhibited perineural invasion, obviously high-risk features. He underwent Mohs surgery of the primary tumor that was performed with uncertain surgical margins, and therefore it was an indication for adjuvant radiation therapy for up to 60 grade that was delivered.

The patient was followed, and unfortunately, the follow-up scans revealed early disease progression with multiple pulmonary nodules. At the time, he was started on systemic therapy with the combination of carboplatin and paclitaxel, receiving 3 cycles. He had follow-up imaging, which showed stable disease. A few months later, repeat imaging showed disease progression in terms of pulmonary nodules and multiple lymphadenopathies, including mediastinal, left and right axillary, as well as evidence of bone metastases. Dr Wong, historically, how have these patients with metastatic cutaneous squamous cell carcinoma have been managed?

Deborah J. Wong, MD, PhD:Unfortunately, historically we’ve had very few systemic treatment options for patients with cutaneous squamous cell carcinoma and actually not that much data either. Much of the data that we use to inform our practice for treatment [were] extrapolated from how we manage squamous cell carcinomas that arise elsewhere, specifically in other areas of the head and neck. Historically, cytotoxic chemotherapy with a platinum-based chemotherapy regimen, much like this patient received, would have been our standard of care. Beyond that, anti-EGFRtherapies such as cetuximab would have also been a consideration.

Ahmad Tarhini, MD, PhD:Dr Emerick, what is the role of surgery in patients with metastatic disease?

Kevin S. Emerick, MD:The role is certainly limited, but it’s not 0. It’s a little more nuanced. We could think about the patients we talked about that have had a solid organ transplant, are not a candidate for immunotherapy, and perhaps have an isolated lung metastasis that may very well be resectable with very acceptable morbidity that may offer good long-term disease control. This disease is different from melanoma, for example. An isolated lung metastasis does not, perhaps, have the same look ahead into the future of multiple liver and lung metastases. Surgical resection in a patient like that is not unreasonable to consider when there are not good systemic options because of their other medical comorbidities.

We also see patients who have a combination of regional and distant metastasis. Some of those regional metastases can also be highly symptomatic. They can cause wounds, they can cause pain, and it may take a few months, several weeks before that immunotherapy might work—if it’s going to work. For symptom relief and disease control, there may still be a role for considering surgical resection. That obviously has to be done within the context of a multidisciplinary team.

I would say the last potential role is the patient with intransient metastatic disease, as we think about the different phases of metastatic disease. Many of these patients can be quite frail. For some of our patients who are transplant eligible, who have a localized intransient metastasis and no other sites of disease, while we know that surgery is not going to cure that patient, it may provide some good local regional control. This may be for only 3 months, perhaps only 6 months, or maybe longer. But in the right patient, who perhaps does not want to pursue other treatments in the form of radiation or systemic therapies, that may be a viable option. That may be a quick outpatient surgical procedure that takes 30 minutes and can actually provide some benefit to that patient. So it’s much more nuanced, and it’s a more limited patient population. But that again is the benefit of having multidisciplinary discussion for this patient population.

Ahmad Tarhini, MD, PhD:Absolutely. Obviously, there’s a role for radiation therapy in these patients, especially if we have symptomatic patients with bone metastases and that’s part of this multidisciplinary discussion as well. Dr McKean, at this point, what are the systemic options for patients upon disease progression? How do we treat them today?

Meredith McKean, MD:Today, with the advent of cemiplimab, an immune checkpoint inhibitor, I think that would be the first option for treatment. As we’ve discussed, for either patients who have had transplants or other patients who you don’t think would tolerate immune checkpoint inhibitors, the other option would be systemic chemotoxic agents. However, with the data that we’ve had in the past, the PFS [progression-free survival] for those is very limited. I think in this setting the first-line treatment would be cemiplimab.

Ahmad Tarhini, MD, PhD:That’s good. This leads us back to the phase II EMPOWER-CSCC-1 study that Dr Emerick introduced and discussed the study design. This study had a group of patients with metastatic disease, either distant metastases or inoperable regional lymphadenopathy that were included and treated with cemiplimab. The dosage was 3 mg/kg every 2 weeks intravenously, up to 96 weeks, and they had tumor imaging assessing response every 8 weeks. They followed RECIST criteria for this patient population. We have the same key inclusion criteria in terms of safety—obviously organ function and ECOG performance status of 0 or 1. In terms of the exclusion criteria, most importantly this was the lack of autoimmune disease, organ transplant, and so on for patient safety.

In the original publication in theNew England Journal of Medicinelast year, there was a response rate in 28 of 59 patients, so it was 47% response rate at a median follow-up of 7.9 months. The response duration of more than 6 months was seen in about 57% of patients. At the time of the publication, 82% of patients had continued response on treatment.

For this patient on our case, he was started on cemiplimab. They used the flat [dosage] of 350 mg every 3 weeks intravenously for 3 cycles. Repeat imaging with a PET [positron emission tomography] or CT [computed tomography] scan showed significant reduction in the signs and metabolic activity of the right and left axiliary lymphadenopathy as well as the mediastinal lymphadenopathy. The pulmonary nodules also had considerable reduction in size.

Transcript edited for clarity.