New Treatment Approaches for Actinic Keratoses

In his Dermatology Week 2022 session, “New Approaches to the Treatment of Actinic Keratoses,” Mark Lebwohl, MD, started by sharing the epidemiology of actinic keratoses, which are “the most common dermatologic diagnosis in patients 45 years of age and older in the United States.” In 2006, there were an estimated 5.2 million visits for actinic keratoses. Prevalence is rising, with a 14.6% increase in the number of treated actinic keratoses per 1000 Medicare patients between 2007 and 2015.

Actinic keratoses are treated to “prevent their development into squamous cell carcinomas [SCCs],” explained Dr Lebwohl. He added, “There is more than ample evidence pointing to the develop or the transition from actinic keratosis to SCC.”

Dr Lebwohl then summarized selected study results regarding the contiguous nature of actinic keratoses and SCCs:

• Seventy two percent of SCCs were contiguous with actinic keratoses.
• Forty four percent of primary lesions were found to be contiguous.
• Sixty six percent of well or moderately differentiated lesions were found to be contiguous.

He continued with the Veterans Affairs Topical Tretinoin Chemoprevention Trial, noting that “the risk of progression of actinic keratosis to SCC was 0.60% at 1 year and 2.57% at 4 years,” with “65% of all primary SCCs and 36% of all primary basal cell carcinomas [arising] in lesions previously diagnosed clinically as actinic keratoses.” This trial also showed some spontaneous resolution of actinic keratoses, with “55% of actinic keratoses that were followed clinically not present at the 1-year follow up [and] 70% not present at the 5-year follow up.”

“Inflammation is associated with [the] progression of actinic keratoses to SCCs,” stated Dr Lebwohl. “You start out with an asymptomatic actinic [keratosis], it becomes an inflamed actinic [keratosis], which then becomes an SCC. So, there is a stepwise loss of differentiation,” he said.

Next, Dr Lebwohl reviewed treatments used for actinic keratoses, including:

• Cryotherapy
• 5-fluorouracil (5-FU)
• Imiquimod
• Ingenol mebutate

“One of the drawbacks of cryotherapy,” he said, “is that at 1 year, only 4% [of patients] are completely clear. 5-FU, likewise, only 33% are clear at 12 months.”

He moved on to discuss topical 3% diclofenac in 2.5% hyaluronan gel to treat actinic keratoses, normally administered over 90 days. In a study comparing diclofenac gel with 5-FU, it was shown that “diclofenac was less irritating.”

He also touched on imiquimod as a treatment, pointing out that “the mean reduction [of actinic keratoses lesions] using a twice a week application of imiquimod was 83.3%.”

Ingenol mebutate is no longer on the market; however, tirbanibulin can be used. It is a potent tubulin polymerization and Src kinase inhibitor that works by a novel mechanism of action. Dr Lebwohl noted the efficacy of tirbanibulin at day 57, “Forty four percent of the tirbanibulin patients cleared completely [in the first trial] and 54% [in the second trial].” In terms of partial clearance, 68% of patients treated with tirbanibulin had 75% or greater clearance at day 57 in the first trial and 76% in the second trial. “These numbers are actually superior to ingenol mebutate,” he concluded.

The safety results for tirbanibulin are promising, with no serious adverse events for patients receiving tirbanibulin in the first trial and only one adverse event in the second trial. Fewer than 10% of study participants receiving tirbanibulin had severe local skin reactions. Tirbanibulin is now FDA approved and can also be used to eradicate periungual SCC. Dr Lebwohl remarked, “Knowing that [this] drug can work for SCCs is helpful and hopefully we’ll get more information proving that.”

In closing, Dr Lebwohl cautioned that the cost of tirbanibulin has been a problem. It can cost patients upwards of $1000. Negotiated prices with the pharmaceutical manufacturer can result in significant savings for patients. “You really have to check at individual pharmacies to find out what the cost is,” he recommended.

Reference

Lebwohl M. New approaches to the treatment of actinic keratoses. Presented at: Dermatology Week 2022; May 11–14, 2022; Virtual.