There is a strong rationale for using immunotherapy to treat nonmelanoma skin cancers (NMSCs) such as Merkel cell carcinoma (MCC) and cutaneous squamous cell carcinoma (cSCC), according to a study published in the American Society of Clinical Oncology Educational Book.

In this review of recent discoveries in the biology of NMSCs, researchers focused on the emerging importance of immune mechanisms in the pathogenesis of these cancers. Specifically, researchers sought to better understand MCC pathogenesis and immunology of cSCC and basal cell carcinoma (BCC), based on recent epidemiological findings of strong links between NMSCs and immunosuppression.

In patients with MCC being treated with PD-L1 inhibitor avelumab, the response rate was 33% after ≥1 year of follow-up, and 1-year survival was 52%. When avelumab was subsequently tested in treatment-naive patients with MCC, the response rate was 62% compared with patients whose disease had progressed on or after chemotherapy. In a phase 2 study, patients with unresectable or metastatic cSCC had an overall response rate of 28%. PD-1 blockade has also been investigated in a phase 1/2 study of patients with advanced or metastatic cSCC, in which the response rate was 47% exceeding 6 months in duration. Due to the elevated tumor mutational burden in BCC, there is emerging interest in using immunotherapy for patients who are Hh-refractory or intolerant of Hh inhibitors. Anecdotal observations of some completed and durable responses after treatment with cemiplimab, nivolumab, and pembrolizumab in patients with metastatic BCC have led to a variety of ongoing clinical trials with these PD-1 antibodies.

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“The frequent and durable responses to PD-1/PD-L1–blocking antibodies confirm the importance of immune mechanisms in NMSC pathogenesis,” the researchers concluded. “However, not all patients experience a response to immunotherapy, and some develop secondary resistance. Thus, a key question remains as to what tumor or host characteristics might be used to predict response and/or resistance. In addition to finding predictive biomarkers, there is a dire unmet need for finding effective therapies in immunocompetent patients whose tumors do not respond to PD-1/PD-L1 blockade. Mechanistic studies to understand both intrinsic and acquired mechanisms of resistance are critical to uncover new rational therapies to overcome these.”


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Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Reference

Hall ET, Fernandez-Lopez E, Silk AW, Dummer R, Bhatia S. Immunologic characteristics of nonmelanoma skin cancers: implications for immunotherapy. Am Soc Clin Oncol Educ Book. 2020;40:1-10.