Why Target PD-1 in Advanced cSCC?

Anna C. Pavlick, DO:The primary goal for any cancer patient is really curative-intent therapy. With squamous cell carcinoma of the skin, there have never been any accepted standards of care. We just extrapolated the data from the squamous cell head and neck cancers, which behave very differently, but that was the best we had. We would look at giving patients either combination chemotherapy or radiation. Instead of giving them EGFR receptor inhibitors, you could also give something like cetuximab with or without radiation. However, those therapies were ineffective and also did not provide any durable length of disease control.

As part of the research that was done looking at how we could better improve therapy for squamous cell carcinoma of the skin, we looked at tumor mutational burden. This is because we know that the more mutated a tumor is, the higher the likelihood is that they will have a response to immunotherapy. We also looked at PD-L1 [programmed death-ligand 1] status on squamous cell carcinomas, and the majority of patients with squamous cell carcinoma of the skin had an incredibly high PD-L1 percentage. But these cancers also have high tumor burdens. It made intuitive sense that with a high mutational rate, and a high PD-L1 expression, that these tumors really should be candidates for immunotherapy with a PD-1 [programmed cell death protein 1] agent.

Anti—PD-1 therapy is now the recommended systemic therapy for metastatic or locally advanced cutaneous squamous cell carcinoma of the skin. I think using something like cemiplimab, which is the only FDA-approved anti–PD-1 agent for metastatic squamous cell carcinoma of the skin, would be my first line of therapy, knowing that it has a better than 50% response rate. But it also provides patients with long-term durable control of their disease—something very different from what we’ve seen with chemotherapy or EGFR inhibitor therapy.

Transcript edited for clarity.

Case: A 74-Year-Old Male With Recurrent Metastatic CSCC

November 2017

• A 74-year-old male from Florida, with history of multiple resections of CSCC on neck, back and shoulders presents with new deep lesion that exhibited perineural invasion and c/o palpable left axillary mass
• Imaging confirmed 6cm left axillary nodal conglomerate
• Patient treated with neoadjuvant cisplatin/5FU for 3 cycles
• Surgical resection of primary lesion; Lymphadenectomy revealed CSCC involvement in 12 out of 16 resected lymph nodes

May 2018

• Follow-up scans revealed early disease progression with multiple pulmonary nodules
• Patient started on carboplatin/paclitaxel for 3 cycles

November 2018

• Repeat imaging showed disease progression in pulmonary nodules and multiple lymphadenopathies; mediastinal, left and right axillary; bone metastases
• Patient started on cemiplimab for 3 cycles

February 2019

• Reimaging PET-CT revealed reduction in size and metabolic activity of right and left axillary, and mediastinal lymphadenopathies; pulmonary nodules had considerable reduction in size and were no longer substantial