Novel, Immune Therapies Promising in Nonmelanoma Skin Cancers

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Treatment of keratinocyte carcinomas such as basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) with PD-1 checkpoint inhibitors and targeted agents warrants further investigation, according to a group of recently published studies in JAMA Dermatology.

The first study examined PD-L1 expression in BCC, and using immunohistochemical staining found that among 138 tumors from 62 patients, 124 were positive for PD-L1 expression (89.9%) in tumor cells, and 131 of these BCCs were positive for PD-L1 expression (94.9%) in tumor infiltrating lymphocytes (TILs).

The study also found that the intensity of PD-L1 staining was increased in treated BCCs (n = 78) vs untreated BCCs (n = 60) in both the tumor cells (32% vs 7%; P = .003) and TILs (47% vs 18%; P = .008).

The authors cautioned against generalizing their findings, however. “The BCCs in our study were derived from a specialty nonmelanoma skin cancer clinic enriched for advanced or high-risk BCCs,” wrote lead author Julia Chang, MS, of Stanford University School of Medicine in California. “Therefore, PD-L1 expression in this study may be higher than if the BCCs were drawn from a lower-risk, general dermatology clinic.”

A second study examined the involvement of PD-1 and PD-L1/PD-L2 in cutaneous SCC and presented findings of a single SCC patient with locally advanced disease treated with pembrolizumab.

Using NanoString technology, the researchers examined 38 high-risk cutaneous SCCs from 24 patients for expression of PD-L1 and PD-L2 in the tumor microenvironment. When compared with normal skin specimens, this revealed significant involvement of PD-1 and its ligands, suggesting therapeutic potential.

The patient who received treatment with pembrolizumab had an ulcerated, 4-cm lesion, and had declined radiation therapy or surgery. After 4 cycles of pembrolizumab (2 mg/kg) every 3 weeks the lesion was almost completely eradicated.

The third study looked at the efficacy of the targeted agent cetuximab in advanced cutaneous SCC. Of the 31 cetuximab-treated patients, 2 (6.5%) achieved a complete response, and 13 (41.9%) achieved a partial response. Stable disease was reached in 6 patients (19.4%), with the rest progressing.

With a median follow-up of 19 months, the patients had a median progression-free survival of 9 months and an overall survival of 13 months. The treatment was well tolerated, with no patients requiring a dose reduction.

The study also confirmed the low frequency of NRAS, BRAF, EGFR, HRAS, and KRAS mutations in cutaneous SCC. No patients had mutations in KRAS or BRAF genes. One patient, who harbored an NRAS mutation, achieved a partial response and another, with an HRAS mutation, achieved a complete response.

“Keratinocyte carcinomas have entered the era of targeted therapy as well as immunotherapy,” wrote Edit B. Olasz, MD, PhD, of the Medical College of Wisconsin in Milwaukee, and colleagues in an editorial that accompanied the studies. “We foresee that in the near future, systemic targeted and immunotherapies will be combined with local treatment modalities, such as oncolytic virus therapy, radiotherapy, photodynamic therapy, or topical chemotherapy or immunotherapy.”