Posted by Carla Rothaus
In the two trials by Blauvelt et al., how did tirbanibulin compare with vehicle ointment for the treatment of actinic keratoses on the face or scalp?
Tirbanibulin 1% ointment — a synthetic, antiproliferative agent that binds tubulin, inhibits tubulin polymerization, and disrupts Src signaling in actively dividing cells — is being investigated as a field therapy for actinic keratosis on the face or scalp. In two identically designed double-blind trials, Blauvelt et al. randomly assigned adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. Read the NEJM Original Article here.
Q: Is actinic keratosis a premalignant lesion?
A: Actinic keratosis is a common precancerous condition found on sun-damaged skin, particularly on the face, scalp, arms, and legs. In the United States, the prevalence of actinic keratosis is approximately 58 million persons, with the condition commonly affecting men, persons with fair skin, persons with a history of prolonged exposure to ultraviolet light, and older persons. Left untreated, actinic keratosis may progress to invasive cutaneous squamous-cell carcinoma; the reported risk of progression ranges from 0.025 to 16% per lesion per year. Given the unpredictable nature of progression, treatment of all actinic keratoses has been recommended.
Q: What are some of the therapies used to treat actinic keratosis?
A: Individual actinic keratosis lesions are typically treated with cryosurgery. Treatment of multiple lesions and surrounding solar-damaged skin (field therapy) includes topical agents (fluorouracil, diclofenac, imiquimod, or ingenol mebutate) and photodynamic therapy. These treatments are associated with local reactions of pain, irritation, erosions, ulcerations, and irreversible skin changes of pigmentation and scarring, and some treatments have to be administered over periods of weeks or months, which may reduce adherence and undermine treatment success.
Morning Report Questions
Q: In the two trials by Blauvelt et al., how did tirbanibulin compare with vehicle ointment for the treatment of actinic keratoses on the face or scalp?
A: In these two phase 3 trials, tirbanibulin 1% ointment, applied by the patient once daily for 5 days, resulted in higher percentages of patients with complete and partial clearance of actinic keratosis lesions than vehicle at day 57. The active treatment was associated with an estimated 47% of the patients with complete clearance having recurrent lesions at the 1-year follow-up. No comparisons can be made between tirbanibulin and other treatments because of differences in trial design and in the populations included in the trials.
Q: How common were severe local reactions in patients who received tirbanibulin in the trials by Blauvelt et al.?
A: Local reactions were mostly mild-to-moderate erythema, flaking or scaling, application-site pruritus, and application-site pain that resolved spontaneously. Unlike with most topical treatments for actinic keratosis, severe local reactions, including vesiculation or pustulation and erosion or ulceration, were infrequent with tirbanibulin ointment. This could be due to the relatively short, 5-day course of once-daily treatment. Systemic adverse events were uncommon, a finding that is consistent with the negligible systemic absorption of tirbanibulin.
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