Tirbanibulin for Actinic Keratosis: George Martin, MD

George Martin, MD.

Recently, the results of two phase 3 trials on tirbanibulin were published in the New England Journal of Medicine. Tirbanibulin was studied in two identically designed double-blind trials as a treatment for actinic keratosis, a precursor of cutaneous squamous-cell carcinoma. Adults with actinic keratosis lesions on their face or scalp received either tirbanibulin 1% ointment or placebo once daily for five consecutive days. Compared with those receiving placebo, patients who received tirbanibulin had significantly higher rates of complete clearance and partial clearance of their lesions. In this interview, George Martin, MD, medical dermatologist at Dr. George Martin Dermatology Associates and one of the study’s authors, speaks with Oncology Data Advisor about the safety, efficacy, and clinical advantages of tirbanibulin for patients with actinic keratosis.

Can we start by hearing some background about actinic keratosis and its relationship to squamous cell carcinoma?

George Martin, MD: Actinic keratoses are premalignant lesions of the skin, and they’re found in fair-skinned individuals who’ve had a lot of sun exposure. We rarely see them in African Americans and people of type five and six skin coloration because they have natural sun protection from melanin. An estimated 10% of women and 25% of men in the United States develop actinic keratoses, and I think that number is probably higher in regions that receive more sunlight. Actinic keratoses are premalignant, and they can evolve into invasive squamous cell carcinoma. Each year, somewhere between 9,000 and 12,000 people die from cutaneous squamous cell carcinoma

What led you to research tirbanibulin as a treatment for actinic keratosis?

Dr. Martin: The scientists at Athenex developed a molecule that breaks up the spindle apparatus inside cells, which is where chromosomes line up and get pulled apart into two cells when a cell is dividing. This prevents growth of rapidly dividing cells like those that make up actinic keratosis lesions. The idea that you could develop a cream with that molecule and destroy a rapidly dividing precancerous cell made this a really enticing molecule for development, and that’s exactly what happened.

In your study, patients who used tirbanibulin had significant reduction of lesions at two months. Can you comment on the significance of that?

Dr. Martin: So we think about tirbanibulin in terms of a field therapy. The standard therapy for individual actinic keratoses on the face, scalp, trunk, or extremities is to freeze them with liquid nitrogen and destroy them. But in many cases, there are too many to freeze, so we have to employ what we call field therapy, a cream or treatment that treats an entire area. It could be a full face or a full scalp or the decollate, chest, or forearms. We employ things like 5-fluorouracil (5-FU), diclofenac, and imiquimod, or we use a photo sensitizing liquid combined with light to destroy these actinic keratoses. The problem is that some of these treatments take weeks, and the downtime can be weeks and sometimes months. It’s hard to work and carry on a normal daily life because the longer you treat with these molecules, the more aesthetically unsightly you become with crusting and erosion at lesions. The amount of irritation has people take days or weeks off work while they go through the treatment. In many cases, at the end of the treatment, there’s another week of healing as the crust and erosions—and sometimes ulcerations and the redness—subside. It’s like your worst sunburn.

Now tirbanibulin is a once-a-day, five-day treatment, and it has clearance that’s as good as or better than any other field therapy out there, including 5-FU, imiquimod, and photodynamic therapy (PTD). When we look at the irritant profile of the treatment, the irritancy is maybe on average 3 to 4 on a scale of 18, which is remarkable for this treatment. Severe side effects are also very uncommon, 1% or 2%. We really have a new field therapy that allows you to treat over five days and is very safe and efficacious. It’s more likely to be adopted not only by patients who use it, but also physicians who treat, because compliance is a big issue with some of these lengthy treatments, as you might imagine. This treatment is five days, and then you’re done. It’s a once-a-day treatment, which is really nice because you put it on at bedtime, go to sleep, and it works while you sleep.

How can clinicians use your findings to improve patient care?

Dr. Martin: The data tell us that patients with actinic keratoses often leave the office without a field therapy because of issues regarding compliance with the currently used therapies. Less than 20% of patients are prescribed a field therapy, despite the fact that they need it. They have individual lesions frozen, but the entire field is not treated, because of side effects and noncompliance. When patients treat with some of these other therapies, they call back after the end of treatments with concerns that they think they’re infected, they’re sore, they can’t sleep, or they just don’t feel well. What tirbanibulin does is it gives us a very safe and efficacious short-course treatment that causes minimal irritation to the skin.

Tirbanibulin really answers so many of the needs that we as dermatologists have in our checklist of things we want in a field therapy to treat actinic keratosis. Number one, we want something that’s highly efficacious, and tirbanibulin is as good or better than anything out there as a field therapy. Number two, it’s incredibly safe with a really great irritation profile. It’s a once-a-day, five-day treatment; the current FDA-approved treatments range from one week to 90 days of treatment, and with most cases it averages about four to six weeks of treatment or in the case of PDT, an in-office treatment but a week of downtime.

Is there anything else you would like to add today?

Dr. Martin: I think this is going to be a game changer molecule for the treatment of actinic keratosis, because it checks all the boxes that we as prescribing dermatologists, nurse practitioners in dermatology, and physician assistants in dermatology want to see. We have a therapy that is short term, once-a-day, highly efficacious, very safe, and minimally irritating. That’s likely to lead to really good patient compliance, and clinicians are more likely to prescribe. The caveat in all of this is that actinic keratosis is a chronic disease and once you treat the field, over the course of time, new lesions tend to pop up. So we’re treating on an ongoing basis.

I’ll leave you with one last thought. Individuals who cleared their entire 25 cm2 field in the clinical trials were asked to follow up in one year to see how many lesions came back, and approximately half of the patients had none of their original lesions come back. So we know this is a durable response. The other half of patients had only one or two of the original four to eight lesions recur. Patients did, however, develop new actinic keratoses, and that’s consistent with the chronic nature of this disease. So as clinicians are monitoring their patients at least once or twice a year, if new actinic keratoses show up, we now have a treatment that patients are more likely to embrace.

About Dr. Martin

George Martin, MD, is a medical dermatologist at Dr. George Martin Dermatology Associates in Kihei, Maui, Hawaii. He is American Board Certified in both dermatology and internal medicine and is a practicing clinician, clinical investigator, and internationally recognized lecturer. Dr. Martin’s areas of interest include cutaneous oncology, psoriasis, atopic dermatitis, acne, and connective tissue disorder diseases.

For More Information:

Blauvelt A, Kempers S, Lain E, et al (2021). Phase 3 trials of tirbanibulin ointment for actinic keratosis. N Engl J Med, 384(6):512-520. DOI:10.1056/NEJMoa2024040

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor.

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