• Andrew Blauvelt, Steven Kempers, Edward Lain, Todd Schlesinger, Stephen Tyring, Seth Forman, Glynis Ablon, George Martin, Hui Wang, David L Cutler, Jane Fang, Min-Fun R Kwan, and Phase 3 Tirbanibulin for Actinic Keratosis Group.
• From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).
• N. Engl. J. Med. 2021 Feb 11; 384 (6): 512-520.

BackgroundThe tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma.MethodsIn two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. The ointment was applied by the patients to a 25-cm2 contiguous area containing four to eight lesions once daily for 5 consecutive days. The primary outcome was the percentage of patients with a complete (100%) reduction in the number of lesions in the application area at day 57. The secondary outcome was the percentage of patients with a partial (≥75%) reduction in the number of lesions within the application area at day 57. The incidence of recurrence was evaluated at 1 year. Local reactions were scored with the use of 4-point scale (ranging from 0 [absent] to 3 [severe]).ResultsA total of 702 patients were enrolled in the two trials (351 patients per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; P<0.001); in trial 2, the percentages were 54% (97 of 178 patients) and 13% (22 of 173), respectively (difference, 42 percentage points; 95% CI, 33 to 51; P<0.001). The percentages of patients with partial clearance were significantly higher in the tirbanibulin groups than in the vehicle groups. At 1 year, the estimated percentage of patients with recurrent lesions was 47% among patients who had had a complete response to tirbanibulin. The most common local reactions to tirbanibulin were erythema in 91% of the patients and flaking or scaling in 82%. Adverse events with tirbanibulin were application-site pain in 10% of the patients and pruritus in 9%, all of which resolved.ConclusionsIn two identically designed trials, tirbanibulin 1% ointment applied once daily for 5 days was superior to vehicle for the treatment of actinic keratosis at 2 months but was associated with transient local reactions and recurrence of lesions at 1 year. Trials comparing tirbanibulin with conventional treatments and that have longer follow-up are needed to determine the effects of tirbanibulin therapy on actinic keratosis. (Funded by Athenex; ClinicalTrials.gov numbers, NCT03285477 and NCT03285490.).Copyright © 2021 Massachusetts Medical Society.

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