Immune Checkpoint Inhibitors for Cancer Treatment Tied to Significant Reduction of Actinic Keratoses: JAMA

These findings, published in JAMA Dermatology, suggest that ICIs may serve as an immuno-preventive strategy for high-risk individuals.

The researchers note that keratinocyte carcinomas (KCs), including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), are the most common human cancers. Actinic keratoses (AKs) are precursors to cSCC, with a higher risk in patients with extensive lesions due to field cancerization. Immune checkpoint inhibitors improve survival, however, their preventive potential remains uncertain. Considering this, Charlotte Cox, University of Queensland, Brisbane, Australia, and colleagues aimed to assess the impact of immune checkpoint inhibitors (ICIs) on field cancerization by comparing the number of AKs and KCs at baseline and 12 months after initiating ICI therapy.

For this purpose, the researchers conducted a prospective cohort study at a tertiary public hospital in Brisbane, Australia, from April 2022 to November 2023. Immunocompetent adults initiating programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PDL-1) inhibitor therapy for active cancer, with a planned treatment duration of at least six months and clinical actinic keratoses on their forearms, were included. Those with immunosuppression, concurrent chemotherapy or radiotherapy, or recent topical fluorouracil use were excluded.

AKs were counted and photographed at baseline and three, six, and twelve months, while keratinocyte carcinoma numbers were assessed using histopathology reports. Participants’ medical history, cancer response, and adverse events were recorded.

Key Findings:

• The study included 23 participants, with 73.9% being male and a mean age of 69.7 years.
• No participants withdrew, but four died due to disease progression.
• The mean number of actinic keratoses (AKs) significantly decreased from 47.2 at baseline to 14.3 at 12 months.
• Younger patients were more likely to reduce AKs by 65% or more (66.7% versus 33.3%).
• Patients with a history of blistering sunburn had a 100% likelihood of reducing AKs by 65% or more.
• Total keratinocyte carcinoma (KC) numbers decreased from 42 before ICI therapy to 17 in the year after.
• Cutaneous squamous cell carcinoma cases declined from 16 to 5 over the same period.

“These findings suggest that immune checkpoint inhibitors, originally used for cancer treatment, may help mitigate field cancerization as an immunopreventive strategy in high-risk populations,” the researchers stated. They further noted, “While ICIs significantly reduced clinical actinic keratoses (AKs), the decline in cutaneous squamous cell carcinomas was not statistically significant.”

Concluding their findings, they emphasized, “Given the potential for life-threatening adverse events, these results highlight the need for future clinical trials to explore ICIs’ role in preventing keratinocyte carcinomas in individuals at extreme risk, particularly when other preventive options are not feasible.”

Reference:

Cox C, Brown S, Walpole E, et al. Immune Checkpoint Inhibitors in Field Cancerization and Keratinocyte Cancer Prevention. JAMA Dermatol. Published online February 12, 2025. doi:10.1001/jamadermatol.2024.5750